CANADIAN ASSOCIATION OF PATHOLOGISTS | ASSOCIATION

CANADIENNE DES PATHOLOGISTES

ABSTRACTS – RÉSUMÉS

JUNE 4-8, 2011

62ND ANNUAL MEETING

VANCOUVER, BRITISH COLUMBIA

4-8 JUIN 2011

62IÈME ASSEMBLÉE ANNUELLE

VANCOUVER, COLOMBIE-BRITANNIQUE

Oral Presentatons

O211HISTONE DEACETYLASE 1 AND 2 IN MESENCHYMAL TUMORS.

M. Pacheco, T.O Nielsen. Department of Pathology and Laboratory Medicine,

University of Britsh Columbia, Vancouver, Britsh Columbia.

Objectve: Histone deacetylases (HDACs) are a group of enzymes implicated in

epigenetc gene silencing, a mechanism of transcriptonal regulaton important in

the pathogenesis of many sof tssue sarcomas associated with translocatons. The

efcacy of HDAC inhibitor drugs has been proven preclinically in this type of tumor

and has inspired a Canadian clinical trial (IND.200). Nevertheless the in situ

expression of their target HDAC proteins has not been comprehensively assessed

in surgically-excised mesenchymal neoplasms. The aim of this study is to survey

the immunohistochemical expression of HDAC1 and 2 in a large collecton of

mesenchymal tumors and tssues, to assess if there is high expression of HDAC

isoforms in translocaton-associated sarcomas that supports their sensitvity to

this class of drugs. Methods: In-situ expression of HDAC1 and 2 was surveyed by

immunohistochemistry in 2169 specimens spread over 10 tssue microarrays

representng 74 categories of malignant and borderline mesenchymal neoplasms

and 40 normal tssues that were included in the analysis. A score system was

established based on percentage of tumor cells stained and intensity of staining,

resultng in a fnal score from 0-6. Comparison of the distributon of the staining

scores between groups was made using the Wilcoxon rank-sum test. The

proporton of tumors expressing HDAC1 and HDAC2 was compared using

Pearson’s chi-square test. A p< 0.05 was considered statstcally signifcant.

Data and Results:

Specimen group: normal

tssues

translocaton-associated

sarcomas

other mesenchymal

neoplasms

total # specimens 136 217 986

HDAC1, mean[+/- 95% CI] 1.7 0.8 [0.6-1.0]* 1.6 [1.4-1.7]

HDAC2, mean[+/- 95% CI] 3.9 4.6 [4.4-4.8]** 3.7 [3.6-3.8]

Asterisks denote signifcantly *less than or **greater than normal tssues, p<0.05 (Wilcoxon)

Conclusions: HDAC2 is present and intensely expressed in a very high proporton

of mesenchymal tumors, and partcularly among sarcomas associated with fusion

transcripton factors being assessed in IND.200. HDAC1, consistently with the

literature, is less expressed than HDAC2 in normal tssues, and appears even lower

in mesenchymal tumors. Results support the choice of HDAC inhibitor SB939 in

IND.200, as it has actvity against HDAC2. Tissue from accrued patents will be

assessed for HDAC expression using these assays, and correlated with drug

response.

O212MEMBRANOUS EXPRESSION OF PHOSPHO-EZRIN/RADIXIN/MOESIN (ERM)

PROTEINS: A POTENTIAL BIOMARKER FOR TRIPLE NEGATIVE BREAST CANCER.

S. Varma 1 , A. Day1, J. Cass2, V. Hoskin2, B. Starova2, H. Mak2, A. Rajput1, L. Rapts, Y.

Madarnas3, S. SenGupta1, B. Elliot2. 1Pathology & Molecular Medicine, Queen's

University, Kingston, Ontario; 2Cancer Biology & Genetcs, and 3NCIC-CTG, Cancer

Research Insttute, Kingston, Ontario.

Background: Ezrin is a member of the ezrin/radixin/moesin (ERM) family and has

apical expression in normal breast lobules, but, strong cytoplasmic expression in

breast carcinomas. Another ERM protein, moesin, is a distnguishing marker of

triple negatve (ER/PR/Her2 -ve) breast cancers. We postulate that the actvated

forms of ezrin and/or moesin may have a beter predictve power and therefore, we

examined the expression of actvated ERM proteins (pTERM) in breast cancers.

Design: A TMA from 63 breast cancers (16% triple -ve) and 20 mammoplastes was

made. IHC was performed with antbody for pTERM (which shares epitope

specifcity with ezrin pT567 and moesin pT558). The % of positve area and staining

intensity were scored by two evaluators independently. Cases were dichotomized

into triple -ve versus all other subtypes. pTERM staining was categorized as -/+ and

analyzed using two-sided exact Fisher test. Double immunofuoresence was also

performed on a smaller TMA of 8 triple -ve cases to assess the co-localizaton of

ezrin and moesin. Results: pTERM showed contnuous membranous staining in 19%

of cancers, whereas only apical in normal lobules. A statstcally signifcant

associaton of pTERM with triple -ve cases was observed; the prevalence of triple

-ve cases was 42% in the pTERM +ve and 10% in the -ve cases (p<0.017). Double IF

staining showed striking cytoplasmic co-localizaton of ezrin and moesin within the

tumour cells; in contrast to reports of other breast cancers wherein moesin localizes

to the stroma and ezin remains in tumour cells. Conclusion: The unique associaton

of membranous pTERM in triple -ve breast cancers suggests that the presence of

actvated ERM proteins may be a distnguishing feature of triple-ve breast cancers.

O213

BASAL-LIKE CARCINOMAS OF THE BREAST IN ASSOCIATION WITH TUMORAL

STROMAL FIBROSIS, TUMORAL FIBROSIS NEOANGIOGENESIS, AND

INTRATUMORAL LYMPHOVASCULAR INVASION.

K. Chung, J. Hanson, S. Silverman. Department of Laboratory Medicine,

Misericordia Hospital, Edmonton, Alberta.

Objectves: We hypothesize that tumoral fbrosis, intratumoral lymphovascular

invasion and tumoral neoangiogenesis in basal-like carcinomas (BLC) are

predictors of distant metastases via hematogenous spread. Methods: We

evaluated 11 cases of BLC and 16 controls of invasive ductal carcinoma not

otherwise specifed (IDC NOS) for tumor focality, tumor size and grade, lymph

node status, presence or absence of central and peripheral tumoral fbrosis,

presence or absence of intra and/or peritumoral lymphovascular invasion, tumoral

neovascular density, and breast biomarkers. We performed

immunohistochemistry (IHC) using D240/P63, CD31, and CD5/6 antbodies.

Results: Tumor stromal fbrosis was identfed in 91% of BLC and in 6% of the

controls (p < 0.001). Intratumoral lymphovascular invasion was identfed in 82%

of BLC and 19% of the controls (p = 0.002). The other associatons for BLC and IDC

NOS were not statstcally signifcant. All the cases, including BLC and control cases

showed CD31 positvity in the tumoral fbrosis or central aspect of IDC NOS.

Conclusions: The above fndings show that BLC is associated with tumoral fbrosis,

tumoral neoangiogenesis, and intratumoral lymphovascular invasion. These

histological features may be markers of hematogenous patern of distant

metastatc spread. We are unclear of the fndings associated with CD31 and their

signifcance.

O214P16 EXPRESSION IN ENDOMETRIAL CLEAR CELL CARCINOMA.

J.I. Malowany, R.G. Stovel, S. Nofech-Mozes, R.S. Saad. Department of Pathology

and Laboratory Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario.

Clear cell carcinoma (CCC) of the endometrium is a rare neoplasm and ofen

associated with an aggressive clinical behavior and poor outcome. Furthermore,

the molecular pathways involved in the development of CCC are stll unclear. Both

uterine serous and CCC characteristcally express p53, suggestng that they may

share common molecular pathways. Recent studies have shown that p16 is widely

expressed in the majority of serous carcinoma. However, there is no/minimal data

available regarding p16 expression in CCC. In this study, we investgated the

expression of p16 in endometrial CCC. Forty fve cases of endometrial CCC and 50

endometrial serous carcinomas were retrieved from the archives of anatomic

pathology during the period between January 2002 and December 2010 and a

representatve block was chosen for p16 staining. P16 was considered positve

when tumor showed both nuclear and cytoplasmic staining. Percentages of cells

staining was recorded as follow: Negatve (0-5%), weak (1+, 6-25%), moderate (2+,

26-50%) and strong (3+, >50%). A case was considered positve if more than 50%

of the tumor cells were stained. Amongst the CCC, 24/45 (53%) presented as pure

CCC and 21/45 (47%) as mixed tumors. The majority of serous carcinomas (48/50,

96%) demonstrated difuse/moderate-strong expression (score 3+, >50%). In the

CCC group, only 9/45 (20%) were strongly positve for p16. In the endometrioid

component of mixed tumors, staining was weak and/or patchy. Interestngly, p16

expression showed a signifcant correlaton with lymph node metastases (r =0.45,

P< 0.001). Our data indicate that p16 may play a role in the tumorigenesis of a

subset of CCC and serve as prognostc marker by its correlaton with lymph node

metastases. In contrast to p53 which is expressed in the majority of clear and

serous carcinomas, p16 is expressed in only a fracton of CCC, indicatng a possible

diferent molecular pathway.

1

O215ASSESSMENT OF CORRELATION BETWEEN p16 INK4a STAINING, SPECIFIC SUBTYPE

OF HPV AND PROGRESSION OF CINI LESIONS; FIRST COMPARATIVE STUDY.

M. Razmpoosh MD 1 , A. Sansregret MD2, L.L. Oligny MD1, D. Bouron-Dal Soglio

MD1. 1Department of Pathology, 2Department of Gyneco-Obstetrics, CHU Sainte-

Justne, Université de Montreal, P Quebec.

Objectve: To confrm the interest of p16INK4a staining as a prognostc marker in

cervical intraepithelial neoplasia grade I (CINI), -to compare p16INK4a

immunostaining, specifc subtypes of HPV and evoluton of CIN1 in order to adapt

patent follow up. Method: 74 cervical biopsies with a histologic diagnosis of CINI

were reviewed. CINI diagnosis was confrmed and they were stained with p16INK4a.

HPV status was assessed for 38 of these cases by PCR-direct sequencing, using the

same parafn-embedded specimens. The results of the follow up biopsies were

noted in order to determine the progression of the CINI lesions according with the

p16INK4a and the HPV subtypes. Results: Out of the 74 CINI biopsies, 50 were p16

negatve, of which 19 regressed and 19 remained the same; none progressed. 12

were lost to follow up. Out of the 24 p16 positve biopsies, 10 were lost to follow

up, 3 regressed, 8 remained the same, and 1 progressed. 6 diferent high risk HPV

subtypes were identfed in 7 of the 24 p16 positve lesions (HPV39 was observed

twice). 16 subtypes (12 high risk and 4 low risk) were found in 26 of the 50 p16

negatve samples. Conclusion: We confrm that p16INK4a negatve CINI seldom

progress to a CINII-III lesion. In our series, p16INK4a positve CINI were only

associated with high risk HPV subtypes, whereas both high and low risk HPV were

detected in p16INK4a negatve CINI lesions.

O216NEUTROPHIL DNA NET FORMATION IN APPENDICITIS AND OTHER ACUTE

INFLAMMATORY CONDITIONS.

D. Salina 1,2 , C. Gwozd1,2, F.H. Pilsczek1, F.H.Y. Green1,2, P. Kubes1,3, M. Kelly1,2. 1Snyder Insttute of Infecton, Immunity and Infammaton, 2Department of

Pathology and Laboratory Medicine.

Background: Neutrophil extracellular traps (NETs) are webs of DNA covered with

antmicrobial molecules that consttute a newly described killing mechanism in

innate immune defense (Brinkmann et. Al, Science 2004 Vol. 303). NET formaton

involves a complex process of nuclear envelope breakdown and extracellular

release of DNA and granular enzymes (J.Immunol. 2010 Vol. 185). Objectves: The

purpose of this study was to confrm NET formaton in appendicits and also to

identfy the spectrum of NETs in various acute infammatory conditons.

Methods: Neutrophils were purifed from humans, actvated with S. aureus and

then fxed at various tme points for TEM. TEM images from the in vitro study

were correlated with those obtained from human appendicits. Cases of purulent

appendicits, cholecystts, pneumonia and random abscesses were selected for

analysis based on light microscopy fndings suggestve of NET formaton.

Immunofourescence against histones and granular enzymes was used to detect

NETs. Results: TEM showed an extensive release of numerous DNA containing

vesicles and NETs with lysis of collagen fbers in appendicits. These changes seen

are similar to previously published in vitro studies. The NETs formed in these

tssues, and other acute infammatory conditons, are positve for histones and

neutrophil proteolytc enzymes (including elastase, myeloperoxidase and

lysozyme). Conclusion: Neutrophils form DNA NETs from a highly complex

process when actvated by S.aureus and other bacteria. This includes nuclear

envelope breakdown, exocytosis of DNA containing vesicles, and NET formaton.

The release of NETs is likely harmful to the surrounding tssues, and causes

destructon of collagen fbers. This mechanism is an important part of the acute

infammatory response to microbial infecton, and likely plays a major role in

suppuratve appendicits and other infammatory disorders.

O221THREE-DIMENSIONAL RECONSTRUCTION OF AN ORGANIC STRUCTURE FROM

HISTOLOGICAL SLICES.

B. Falkenberg1,S. Lozanof2, L. Hornberger3, C. Sergi4. 1Dept. of Engineering,

University of Alberta, Edmonton, Alberta; 2Dept. of Anatomy and Reproductve

Biology, University of Hawai'i School of Medicine, Honolulu, USA; 3Dept. Pediatric

Cardiology, University of Alberta Hospital, Edmonton, Alberta; 4Dept. Of Lab.

Medicine and Pathology, University of Alberta, Edmonton, Alberta.

Background: Three dimensional reconstructons (3D) of morphological structures

provide useful informaton for instructve purposes and animatons. This aim of

this study was to develop three dimensional, interactve models organic structures

from histological sectons. Methods: The image analysis suite Imaris was used

along with the sofware ImageJ produce digital models of 3 diferent embryonic

hearts. A digital camera was used to obtain images of the slices, where afer the

slices were aligned and composited to form a 3D model. Our study also examined

the advantages and disadvantages of this approach of imaging. By analyzing and

cataloguing structural defects in a sample, 3D reconstructon may be used to

improve the understanding of failure modes within a structure such as the heart,

and track the development of congenital defects. Results: Qualitatve

observatons showed that the morphological features of our models may be

comparable with those displayed by ultrasound diagnostcs emphasizing this

technique during regular examinaton. Conclusion: Our data supports the use of

both sofware programs for generatng fles useful for 3D computerized modeling.

O222QUALITY ASSURANCE PROGRAMS FOR HEMATOPATHOLOGY MORPHOLOGY.

ASSESSMENT OF PROGRAMS OF FOUR COUNTRIES.

R. Padmore 1,2 . 1Division of Hematopathology, The Otawa Hospital, Otawa,

Ontario; 2Vice-Chair, QMP-LS Hematology Scientfc Commitee, Toronto, Ontario.

Objectve: Assessment of morphology skills is an integral part of external quality

assessment (EQA). This study assesses hematopathology morphology EQA

programs from four countries. Methods: The author is personally enrolled in

hematopathology morphology EQA programs from Royal College of Pathologists

of Australasia Quality Assurance Program (RCPA-QAP), United Kingdom Natonal

External Quality Assessment Service digital morphology (UK-NEQAS-DM),

American Society for Clinical Pathology CHECKPATH-Hematopathology (ASCP), and

partcipates in Quality Management Program-Laboratory Services (QMP-LS)

through the laboratory workplace. Programs were assessed using defned criteria

including size, access, format, material, evaluaton and feedback. Results: All

programs are available to individual partcipants, including QMP-LS available

through Insttute for Quality Management in HealthCare (IQMH). Materials consist

of 3–20 peripheral blood and/or bone marrow cases/year with 180 (QMP-LS) to

1050 (UK-NEQAS-DM) partcipants. All programs have online data entry.

Partcipaton is available for individual pathologists for all programs or as a

laboratory for 2 programs (RCPA-QAP, QMP-LS). Preferred features are excellent

glass slide sets (RCPA-QAP, QMP-LS, ASCP), quickness of reviewing the scanned

slide (UK-NEQAS-DM), providing the partcipant with ancillary test results for

diagnosis (ASCP) and lymph node morphology cases (ASCP). For all programs

useful features are the assessment of the individual or laboratory performance

compared with other partcipants, educatonal feedback, prompt turnaround

tme, use of clinically relevant cases and rare disorders. Conclusions: EQA

programs vary in features providing the hematopathologist with choice depending

on individual needs and objectves associated with skill assessment and

educaton.

2

O223DIGITAL CYTOPATHOLOGY AND WHOLE SLIDE IMAGING – ITS ROLE IN CYTOLOGY

EDUCATION AND PROFICIENCY TESTING PROGRAMS.

G. Rasty1, A. Park2, S. Crafer3, D. Kuni4, M. Weir5, A.L. Wolfsohn6, L. Yawney2, J.

Gun-Munro2, G. Flynn2. 1University Health Network Toronto, Ontario; 2Mount

Sinai Hospital, Toronto, Ontario; 3Quality Management Program – Laboratory

Services, Toronto, Ontario; 4William Osler Health System, Brampton, Ontario; 5London Health Sciences Centre, London, Ontario; 6Gamma-Dynacare Medical

Laboratories, Otawa, Ontario.

Background: Digital Morphology (Virtual Microscopy) uses computers to review

digitzed images of microscopic preparatons. This technology allows pathologists

and cytotechnologists to review images from any computer and enables

consultaton within and among diferent facilites. Material and Methods: A small

pilot survey was conducted by Quality Management Program Laboratory Services

(QMP-LS) in 2010. The partcipants were asked to download the viewing sofware

Image Scope provided by Aperio. QMP-LS distributed the sofware to 51

partcipants within Ontario. The partcipants were asked to view and analyze eight

digital images obtained from various preparaton techniques and body sites.

Results: Over 85% of partcipant responses matched the assigned value, except for

the conventonal respiratory bronchial wash smear. The results showed that

liquid-based preparaton slides are beter suited for digital microscopy since they

have smaller areas to scan. The image quality and ability to focus on the image

and cells are the two most important factors for digital morphology. One of the

main hurdles was downloading the Image Scope sofware because of hospitals’

and community laboratories’ frewalls, though afer reconfguring frewall and

proxy setngs all partcipants were able to proceed with the survey. Conclusions:

By using digital images, External Quality Assessment (EQA) programs can provide

the means for partcipants to view and interpret microscopic preparatons of small

volume, unique or difcult to obtain patent material for assessment and/or

educaton. The survey comments and feedback will help guide QMP-LS in using

digital morphology. The commitee plans to contnue to explore digital

morphology in future surveys and to remain well informed of advances in digital

morphology.

O224STANDARDS 2 QUALITY – DEVELOPING PATIENT SAFETY CHECKLISTS TO

STANDARDIZE SURGICAL PATHOLOGY PROFESSIONAL PRACTICES.

C.M. McLachlin, J.R. Srigley, K.A. Chorneyko, S.B. Joshi, B. Lemay, C.M. MacMillan,

J.B. Mullen, V.A. Tron, V.M. Walley. Path2Quality, Ontario

Background: Path2Quality, a collaboratve initatve of the Ontario Medical

Associaton’s Secton on Laboratory Medicine and the Ontario Associaton of

Pathologists, has developed a draf set of guidelines for internal quality assurance,

focused on professional interpretatve processes. These guidelines include a set of

patent safety checklists (PSCs) analogous to those currently employed by surgical

services to reduce errors in the operatng room. Methods: The surgical pathology

PSCs were developed afer a review of pertnent literature, published quality

assurance guidelines, and regulatory monitoring requirements. The checklists

focus on steps in the interpretve process where critcal hand-ofs and complex

processes need to be optmally accomplished to allow accurate, tmely and

complete reportng. Results: Surgical pathology PSCs delineate steps for intra-

operatve consultaton, gross examinaton, and pre- and post interpretve

practces. The draf quality management program including checklists was

circulated for review to the laboratory physicians of Ontario, as well as to natonal

and internatonal experts. The fnal version of the checklists will include

modifcatons based on this feedback. Conclusions: PSCs have not previously

been published for surgical pathology interpretve practces. The utlity of these

checklists will require feld evaluaton but they have the potental to reduce errors

and clarify expectatons for optmal surgical pathology practces. The checklists

form one component of a comprehensive quality management program for

surgical pathologists.

O225DIGITAL PATHOLOGY: ATTITUDES AND PRACTICES IN THE CANADIAN

PATHOLOGY COMMUNITY.

M. Bellis1, A. Pollet 2, S. Jothy1,3, C. Naugler4, G. Yousef1,3. 1Department of

Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario; 2Department of Pathology and Laboratory Medicine Mount Sinai Hospital,

Toronto, Ontario; 3Keenan Research Centre of the Li Ka Shing Knowledge Insttute,

St. Michael's Hospital Toronto, Ontario; 4Department of Pathology and Laboratory

Medicine, University of Calgary, Calgary, Alberta.

Digital Pathology is a rapidly evolving niche in the world of Pathology and will

likely only increase in popularity as technology improves. By ataining opinions of

Pathologists and Pathology residents across Canada we hope to determine:

1.Their current attudes towards and experiences with digital pathology; 2.Which

modalites digital pathology is best suited for; 3.The need for training in digital

pathology amongst Pathology residents and staf. An online survey consistng of

24 yes/no, multple choice and free text questons regarding digital pathology was

sent out via email to all members of the CAP-ACP and Pathology residents across

Canada. Telepathology (TP) is used in approximately 48% of insttutons, primarily

for teaching purposes (62%), followed by OR/frozen consults (50%). Seventy-two

percent of respondents believe there is a need for TP in their practce. Eighty-fve

percent use digital images in their practce. The top two favoured applicatons of

digital pathology are teaching and consultaton service, with its main advantage

being easier access to cases. The disadvantages of using digital pathology are cost

and image/diagnostc quality. Sixty-fve percent of respondents would atend

training courses in pathology informatcs and 92% think informatcs should be part

of resident training. The results of the survey indicate that Pathologists and

residents across Canada do see a need for telepathology and the use of digital

images in their daily practce where they would be most useful in teaching

environments and consultaton services. Integraton of an informatcs component

into resident training programs and courses for staf Pathologists would be

welcomed.

O226MISMATCH REPAIR IMMUNOHISTOCHEMISTRY USE AMONG CANADIAN

PATHOLOGISTS.

G. Allo 1 , S. Kalloger2, A. Pollet1, A.M. Mulligan1, E. Torlakovic1, B.A. Clarke1. 1University of Toronto, Toronto, Ontario; 2University of Britsh Columbia,

Vancouver, Britsh Columbia.

Background: Mismatch repair immunohistochemistry (MMR-IHC) has recently

been proposed as the primary tool to triage patents with colon (CRC) and

endometrial cancer (EC) for Lynch syndrome screening. The aim of this study is to

determine the current status of MMR-IHC testng in Canada in academic and

community setngs and within specialized referral centres. Methods: Online

surveys of CAP-ACP members and seven referral centres were conducted and

responses analyzed using JMP sofware. Results: Among CAP members (n=74),

there is provincial variaton in access to in house MMR-IHC and to referral centres

(32.33% ± 21.99%, range: 0%-66.67% vs. 61.93% ± 23.12%, range: 40%-100%).

Practce is divergent amongst pathologists and tumour types with regards to

recommending testng or initatng refex testng (50.1% CRC vs. 18.6% EC) and

(21.88% CRC vs. 8.2% EC). Up to 50% consider MMR-IHC as a germline test, but

64% favour using it without consent. 80% of specialist labs classify this as type II

test and partcipate in profciency testng. Only 28% ofer MSI testng. Most

common cases tested are CRC, EC, ovary, gastric and sebaceous carcinomas. There

is lack of consistency in reportng results to pathologists in non-specialist centres.

Conclusion: There is variable availability and practce among Canadian

pathologists regarding MMR-IHC. Consensus guidelines for performance and

reportng should be established.

3

Poster Presentatons

P701TWO UNUSUAL PRESENTATIONS OF CLOSTRIDIUM SEPTICUM AORTITIS.

R. Jacques, M. Gabril, C. McLean, M. Shkrum. The Department of Pathology,

London Health Sciences Centre, London, Ontario.

Background: Clostridium septcum aortts is a rare life-threatening infecton that

has a strong associaton with malignancies, in partcular adenocarcinoma of the

ascending colon. Autopsy case fndings: We present two unusual cases of C.

septcum aortts at autopsy with blood cultures that grew C. septcum. The frst

patent was an 81-year-old man with right scrotal pain. CT scan of the abdomen

was negatve. He died before an exploratory laparotomy could be performed.

Autopsy showed a dilated and dissected aorta, mycotc arterits and thrombosis of

proximal right testcular artery and ischemic colits. No malignancy was identfed.

The second case was an 80-year-old man who presented with nausea and

vomitng. A CT scan of the abdomen showed a mycotc aneurysm and he

underwent a resecton of the infrarenal aortc aneursym, retropertnoeal

debridement plus axillobifemoral bypass. At the completon of surgery he

arrested. At autopsy an occult invasive adenocarcinoma of the terminal ileum was

identfed and confrmed microscopically. Conclusion: We report two additonal

cases of C. septcum aortts, which are rarely reported in the English literature and

review the pathogenesis. The unusual presentatons for these cases are:

epididymits with ischemic colits and adenocarcinoma of the small bowel.

P702

ABNORMALITIES IN THE PRB-CYCLIND1-CDK4/6-P16 PATHWAY IN PRIMARY

SQUAMOUS CELL CARCINOMA OF THE ENDOMETRIUM.

N. Bures MD 1 , M.A. Duggan MD FRCPC1,2, G. Nelson MD FRCSC2, Q. Duan MSc3, A.

Magliiocco MD, FRCPC1,4, D. Demetrick MD PhD, FRCPC1. 1Department of

Pathology and Laboratory Medicine and 2Obstetrics and Gynecology, Faculty of

Medicine, University of Calgary, Calgary, Alberta; 3Clinical Research Unit and 4Translatonal Laboratories, Tom Baker Cancer Centre, Calgary, Alberta.

Objectve: The pathogenesis of primary squamous cell carcinoma of the

endometrium (PSCCE) was recently reported to have abnormalites in the pRb-

cyclinD1-cdk4/6-p16 path independent of the Human Papilloma Virus (HPV). This

study examined PSCCE cases for alteratons in this pathway. Methods: This case

control study, compared cases of PSCCE (n=5) to controls of endometrioid

adenocarcinoma (EADC) with squamous diferentaton (n=8). Expression of H2AX,

pRB p18, p19 CDK6 and HPV 16 by immunohistochemistry (IHC) was

independently scored by two reviewers using the Allred system. Mean scores

based on summed averages of both reviews were calculated for each antbody

and diferences between cases and controls were tested for signifcance using the

Student T test. Results: The mean case and control scores respectvely were H2AX

(7.25, 6.25), pRb (7.25, 7), p18 (2.25, 1.75), p19 (7.5, 7.5), CDK6 (7.5, 6.5) and

HPV16 (0.75, 0). Diferences were insignifcant (p= 0.679). Discussion: Based on

these limited investgatons, the PRB-Cyclin D1-CDK4/6-P16 pathway may play a

role in the pathogenesis of PSCCE. The similarity in expression with EADC; a Type 1

cancer suggests the role is independent of the HPV.

P703MALAKOPLAKIA OF THE LIVER: REPORT OF TWO CASES AND REVIEW OF THE

LITERATURE.

N. Botros MD, S.R. Yan, I.R.Wanless MD. Department of Pathology, Dalhousie

University, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scota, and

Department of Pathology, Dr. Chalmers Regional Hospital, Fredericton, New

Brunswick.

Malakoplakia is an unusual chronic infammatory conditon characterized by the

presence of Michaelis-Gutmann bodies that most commonly afects the

genitourinary tract. It is believed to be associated with an altered immune

response with features of defectve macrophage phagocytosis in response to a

bacterial infecton. Therefore, there is a high incidence of malakoplakia in

immunocompromised patents. Malakoplakia confned to the liver is rare, and

only 5 cases have been described in the literature. We report two cases of

malakoplakia of liver, both were incidental autopsy fndings. The frst case involves

a 53 year old male with systemic lupus erythematosus and chronic refractory

pancytopenia who presented with with severe febrile neutropenia. His blood

culture was positve for Stenotrophomonas and Enterococcus and he

subsequently developed invasive pulmonary aspergillosis. The second case

involves a 60 year old homosexual male who was found to have a mass in

periorbital tssue involving the sphenoid bone which, on biopsy, showed

infammaton and occasional treponema-like spirochetes. He had a sudden

unexpected death at home and autopsy fndings included adrenal gland abscess

and pulmonary edema. Both cases had normal-appearing liver with incidental

microscopic fndings of small, round to oval, solid targetoid structures consistent

with Michaelis-Gutmann bodies. These stained positvely with periodic acid-Schif,

and Von Kossa stain. The frst case also showed numerous hemosiderin positve

granules resembling bacteria singly and in clumps. These might represent

nucleaton sites and an early phase of development of Michaelis-Gutmann bodies.

It is important to be aware of the existence of malakoplakia in unusual locatons.

P704STUDY OF ENDOCERVICAL CURETTAGE IN COLPOSCOPIC EXAMINATION.

F. Siadat, S. Bradshaw, S. Islam. Department of Pathology and Laboratory

Medicine, The Otawa Hospital, University of Otawa, Otawa, Ontario.

Background: Opinions regarding the use of endocervical curetage (ECC) in high

risk female patents range from performing ECC regardless of colposcopic fndings

to omission of the ECC as it may not reduce colposcopic accuracy. Based on one

meta-analysis, published in 1992, the positve and negatve predictve values of

ECC in women who had satsfactory colposcopy were 2.4% and 99.4%,

respectvely. Design: The pathology reports of 310 consecutve female patents

with endocervical curetage performed between 2008 and 2010 were reviewed.

The presence of any other procedure in the same report was noted. This included

cervical biopsy, cone biopsy, and loop electrical excision procedure (LEEP). The

pathology diagnosis of each procedure recorded. Results: In total number of 310

female patents reviewed (mean age of 40.5 years old and SD of 12.1), 234 (75.5%)

had no remarkable pathological fndings. 30 (9.7%) had squamous intraepithelial

lesion (SIL) of any grade. 1 (0.3%) had adenocarcinoma insitu and 2 (0.6%) had

frank adenocarcinoma. In 170 cases, another procedure other than ECC was done.

In this group, only in 2 cases, ECC was reported as low-grade squamous

intraepithelial lesion (LSIL) where the concurrent biopsy was reported as normal.

Conclusion: It appears that ECC may add some additonal diagnostc informaton

when performed in high risk patents. However, the importance and clinical

implicatons require larger and preferably randomized studies.

4

P706microRNA PROFILING IN KIDNEY CANCER: ACCURATE MOLECULAR

CLASSIFICATION OF SUBTYPES AND CORRELATION WITH CYTOGENETIC AND

mRNA DATA.

Y.M. Youssef1,2, N.M.A. White1,2, J. Grigull3, A. Krizova1,2, C. Samy1,2, S. Mejia-

Guerrera1,2, A. Evans1,4, C. Streuther2, G.M.Yousef1,2. 1Department of Laboratory

Medicine and Pathobiology, University of Toronto, Toronto, Ontario; 2Department

of Laboratory Medicine, and the Keenan Research Centre in the Li Ka Shing

Knowledge Insttute, St. Michael’s Hospital Toronto, Ontario; 3Department of

Mathematcs and Statstcs, York University, Toronto, Ontario; 4Department of

Pathology, Toronto General Hospital, Toronto, Ontario.

Objectves: Renal cell carcinoma (RCC) encompasses diferent histological

subtypes. Distnguishing between subtypes is usually made on morphological

basis but this is not always accurate. The aim of this study was to identfy

microRNA (miRNA) signatures that can distnguish between the diferent RCC

subtypes and to explore their biological pathways. Methods: miRNA microarray

analysis was performed on three common RCC subtypes (clear cell, chromophobe

and papillary), and oncocytoma. Results were validated on the original as well as

an independent set of tumors using quanttatve RT-PCR analysis. Results:

Microarray data were analyzed by standard approaches. Relatve expression for

qRT-PCR was determined using the ∆∆CT method and expression values were

normalized to RNU44. We found unique miRNA signatures can distnguish

between the diferent RCC subtypes and also oncocytoma with very high

sensitvity and specifcity. Conclusions: miRNA expression paterns can accurately

distnguish between RCC subtypes. miRNA profles indicate the presence of both

shared and unique pathways among diferent subtypes.

P707

DISTINCT mTOR SIGNALING IN HEPATOCELLULAR CARCINOMA CELL LINES.

M.G. Neuman. In Vitro Drug Safety and Biotechnology Laboratory, and

Department of Pharmacology & Toxicology, University of Toronto, Toronto,

Ontario.

Introducton & Objectves: Hepatocellular carcinoma (HCC) has become the third

leading cause of cancer-related death worldwide, a trend paralleled by an increase

in advanced hepatts C virus (HCV)-related liver disease. Targeted therapies in

HCC have a stellar importance in identfying novel molecular targets for

treatment. Based on its role in cell growth and diferentaton, aim to evaluate

mTOR-signaling actvaton in human HCC cell lines, as well as the ant-tumoral

efect of a dual-level blockade of the mTOR-pathway. Methods: The mTOR-

pathway was assessed using molecular immune and electron microscopy markers.

The efects of dual blockade of mTOR-signaling using everolimus were evaluated

in normal human hepatocytes and liver cancer cell lines HepG2 cells and HuH7 in

the presence or absence of replicon (HCV actve). Results: Aberrant mTOR-

signaling (phosphorylated RPS6) was present in cancer cell lines and was

associated with insulin-like growth factor pathway actvaton, epidermal growth

factor up-regulaton, and changed the tumor cell viability in vitro. Blockage of

mTOR-signaling with everolimus shows a higher apoptotc actvity in replicon cells

when compared with the control HuH7 and HepG2 cells by biomarkers and

electron microscopy. MTor-inhibitor reduced vascular endothelial growth factor

and tumor necrosis factor levels. Conclusions: mTOR signaling has a critcal task in

the pathogenesis of HCC, supportng that mTOR-everolimus blockade is efectve

especially in the HCV-related tumor cells. These fndings establish a ratonale for

targetng the mTOR-pathway in HCC and stratfying the patents based upon their

primary liver disease.

P708

IGG4+ PLASMA CELL INFILTRATION OF COLONIC POLYPS IN AN ASYMPTOMATIC

PATIENT AND OTHER IGG4-RELATED DISEASE CASES.

L.H. Lee 1 , E. Shafer2, S. Urbanski1, M. Kelly1. 1Department of Pathology, University

of Calgary, Calgary, Alberta; 2Department of Medicine, University of Calgary,

Calgary, Alberta.

Objectve: IgG4-related disease (IRD) is a recently recognized disorder, frst

described in relaton to autoimmune pancreatts (AIP), in which numerous IgG4+

plasma cells and fbrosis are present. Non-pancreatc manifestatons have recently

been identfed, but their signifcance is unclear. We report an index case of

colonic polyps infltrated by IgG4+ cells in a patent without evidence of AIP. We

also identfed four additonal cases of IgG4+ cell infltraton in various tssues.

Results: Our patent is a 33 year old female with neurofbromatosis type 1, who

had a single episode of acute pancreatts 12 years ago. Screening colonoscopy,

performed due to a family history of colon cancer, resulted in the removal of two

polyps. Histology showed ulceraton with granulaton tssue and numerous plasma

cells infltratng the submucosa. There were 576 IgG4+ cells/HPF with an IgG4+

/IgG+ cell rato of 80%. The polyp bases showed a fbroblast response. Stains for

neural tssue and gastrointestnal stromal tumor were negatve and there were no

signs of neurofbroma, granuloma, or dysplasia. Her serum IgG4 and autoantbody

levels were normal, and MRCP revealed a normal biliary tree, pancreatc duct, and

pancreas. The other cases of IgG4+ cell infltrated tssues identfed were:

episiotomy granulaton tssue, tssue associated with metastatc adenocarcinoma,

infammatory myoglandular polyp and MALT lymphoma. Conclusions: Various

manifestatons of IRD are stll being described. Our primary patent is unusual as

she is young, asymptomatc, and has no evidence of AIP or autoimmune disease.

The only two cases of IgG4+ polyps previously reported are in elderly symptomatc

patents with AIP. Our cases illustrates that IRD may be more common than

currently reported since they may be asymptomatc and may occur in a variety of

conditons and tssues. IRD may be a manifestaton of a systemic disorder that

requires followup or may represent a localized disease entty that will not

manifest elsewhere.

P709“PROGRESSING” MULTICYSTIC MESOTHELIOMA OF THE LIVER.

M. Caragea 1 , P.M. Smith2, C. Howlet1, J.R. Parft1, T. Krausz3 and S. Chakrabart1. 1Department of Pathology, University of Western Ontario, London, Ontario; 2Department of Pathology, Windsor Regional Hospital, Windsor, Ontario; 3Department of Pathology, The University of Chicago, Chicago, Illinois.

Background: Benign multcystc mesothelioma (BMM) arising in the liver is an

extremely rare lesion that usually afects young women. Only a few cases have

been described to date. Malignant transformaton in a BMM has been reported

only twice. We present a case of BMM arising in the liver, showing evidence of

progression to a malignant mesothelioma. Case presentaton: A 44-year-old

woman presented with a palpable abdominal mass. Her past medical history is

unremarkable. Ultrasound revealed a 10 cm complex cystc mass in the lef lobe of

the liver. A partal liver resecton followed. Grossly, the tumor was composed of

multple cysts containing gelatnous and clear fuid. Microscopically, microcysts

lined by fat or cuboidal cells were set in an edematous and fbrous stroma with

numerous bizarre atypical cells with hyperchromatc nuclei and multnucleaton.

Scatered atypical mitoses were noted. Immunohistochemistry confrmed the

mesothelial origin of both the cells lining the cysts, as well as the stromal cells.

Conclusion: BMM undergoing malignant transformaton is extremely rare; to the

best of our knowledge, this is the third case described. Knowledge that this tumor

may occur in the liver, as well as recogniton of bizarre cytological atypia and

atypical mitoses are helpful to make the diagnosis of a “progressing” multcystc

mesothelioma of the liver.

P710AN UNUSUAL PRESENTATION OF SYNOVIAL SARCOMA, A CASE REPORT.

J. Gruchy MD, MSc; K. Dakin Hache MD, PhD, FRCPC. Dalhousie University,

Laboratory Medicine, Anatomical Pathology Division, Halifax, Nova Scota.

Introducton: Synovial sarcoma accounts for 5 to 10% of sof tssue sarcomas and

over 80% arise in the extremites of younger adults. Primary synovial sarcoma of

the heart is an uncommon entty, and primary pericardial synovial sarcoma is

exceedingly rare with only a few case reports documented. Case History: A 16

year old female presented with a large pericardial efusion. She was otherwise

healthy with only a brief history of generalized malaise. Imaging studies revealed a

5cm solid tumor in the pericardium, medial to IVC at the base of the right

ventricle. There was no evidence of a peripheral primary. Drainage of the efusion

led to fulminant cardiac and pulmonary failure, characterized by worsening

biventricular dysfuncton, severe hypoxia, and end organ damage. She was taken

to the OR and underwent partal resecton of the tumor. During the case, her

cardiac and pulmonary functon was critcal requiring BVAD and ECMO. Cardiac

transplant was considered. Five weeks afer presentaton, she has stabilized.

Results: Gross examinaton revealed a 6.2 cm piece of tan sof tssue with a

homogeneous cut surface. Microscopic evaluaton demonstrated a hypercellular

neoplasm composed of a monotonous populaton of spindle cells arranged in

intersectng fascicles with herringbone confguratons, a rich

hemangiopericytoma-like vasculature, and focal ossifcaton. The nuclei were

closely packed, plump, elongated and mostly blunt ended. An epithelial

component was not identfed. The tumor cells expressed vimentn, CD99, CD56,

bcl-2, and NSE. FISH evaluaton was positve for the loss of the 5’(telomeric) SS18

(SYT;18q11.2) region (93.5%). Molecular evaluaton was positve for SS18/SSX2

fusion transcript by RT-DNA amplifcaton. Conclusion: This report describes a rare

locaton and unusual presentaton of monophasic synovial sarcoma arising in the

pericardium and associated with fulminant cardiac and pulmonary failure.

5

P711PLEURAL MYOPERICYTOMA – A CASE REPORT.

M. Caragea 1 , R. Inculet2, B. Wehrli1, K. Kwan1. 1Department of Pathology, LHSC,

University of Western Ontario, London, Ontario; 2Department of Thoracic Surgery,

LHSC, University of Western Ontario, London, Ontario.

Background: Myopericytoma is part of the spectrum of perivascular tumors,

showing myopericytc diferentaton. It is frequently encountered in the skin and

superfcial sof tssue of the extremites. Rare cases have been described in the

deep sof tssues and in the trunk. We report a case of myopericytoma arising in

the pleura. To the best of our knowledge, a primary pleural myopericytoma has

never been reported. Case presentaton: A 55 year old woman presented with

lef subscapular pain. A subsequent chest CT demonstrated a 1.5 cm nodule

located in the lef pleural base. The wedge resecton specimen showed a well

circumscribed, un-encapsulated tumor composed of a proliferaton of plump oval

to spindle cells with monomorphic nuclei and a prominent concentric perivascular

growth patern with the typical spinning of from the vessel wall. At the periphery

of the lesion multple stag horn vessels were present. Cytologic atypia, mitoses

and necrosis were not noted. The immunohistochemical studies performed

confrmed the myopericytc origin. The neoplastc cells are positve for smooth

muscle myosin and Bcl2. Conclusion: Although myopericytoma is a relatvely

common tumor in the skin and superfcial sof tssue of the extremites, a primary

pleural myopericytoma has not previously been described.

P712LYMPHOMA ARISING IN PAGET’S DISEASE OF BONE – RARE CASE REPORT.

D. El Demellawy MD, PhD, FRCPC. Pathology Department, Northern Ontario

School of Medicine, Sudbury, Ontario. William Osler Health Center, Brampton,

Ontario.

The malignant potental of Paget’s disease of bone is well recognized; however,

primary involvement by lymphoma is extremely rare. We present a rare case of

concomitant occurrence of Paget’s disease of bone and lymphoma. A 94-year-old

male presented with a right hip displaced subcapital fracture. His medical history

is signifcant for limited cardiac functonal capacity, and chronic renal insufciency.

His Peripheral blood shows mild microcytc anemia but no other abnormality.

Imaging reveals lef upper lobe atelectasis and focal sclerosis in the lateral lef 7th

rib but no other aggressive bone lesions. Multple right renal cystc hypodensites

are noted, largest measures 2.4 x 2.2cm. There is a solitary hypointense cyst in the

liver segment 8 measuring 1.1cm. There are multple splenic cystc hypodensites,

largest is at the superior pole with partal thin rim calcifcaton measuring 6.6 x 5.1

cm. No evidence of lympadenopathy or organomegaly. Right hip cemented

bipolar hemiarthroplasty is performed which revealed microscopic evidence of

Paget’s disease of bone and intervening bone marrow involvement by low grade B

cell lymphoma. We present a rare case of synchronous B cell lymphoma and

Paget’s disease of bone occurring in the same site. The absence of peripheral

absolute lymphocytosis, lymphadenopathy, organomegaly and masses raises the

possibility that the lymphoma, in the current case is primary rather secondary.

Though Paget’s disease is known to have malignant potental partcularly with

osteosarcoma, associaton with lymphoproliferatve disorder is extremely rare.

P713DETECTION OF SERINE 105 PHOSPHORYLATION ON ER-β AND ITS CORRELATION

WITH PATHOLOGICAL STATUS OF THE BREAST CANCER.

Y. Liang MD, PhD1, I. Sidiqui MD1, H.-M. Lam PhD2, Y.-K. Leung PhD2, S.-M. Ho PhD2,

J. Wang, MD, PhD1. 1Department of Pathology and Lab Medicine, and 2Department of Environmental Health, University of Cincinnat College of

Medicine.

Estrogen receptor-β has been established as an ant-proliferatve factor in breast

cancer cells. A recently described human ER-β serine105 (S105) phosphorylaton

site was identfed. The current study was to investgate the expression of ER-β

and S105 phosphorylaton in normal breast and breast cancer cells, and correlate

the expression levels with tumor grade and stage. Twenty-fve breast cancer cases

were analyzed by immunohistochemical staining using an antbody specifc to

phosphorylated S105 (pS105) ER-β and using a scoring system similar to Allred

scoring. pS105 signal was localized in both nuclei and cytoplasm of the benign

myoepithelial, luminal secretory, as well as breast cancer cells. A stronger,

however not statstcally signifcant nuclear staining was detected compared to

the cytoplasmic staining. No signifcant diference of pS105 staining was identfed

between breast cancer cells and benign tssues (Nucleus: 7.0±0.1 vs 7.0±0.2;

cytoplasm: 6.6±0.1 vs 6.5±0.3). No correlaton was identfed between pS105

staining intensity and ethnicity, status of ER, PR, Her2/neu, and Ki-67, ER-β

positvity or TNM staging. In contrast, both nuclear and cytoplasmic ER-β1 signal

was signifcantly reduced (p<0.01) in cancer cells vs. adjacent benign epithelium.

Since S105 is common in all ER-β isoforms (β1-5), the increased phosphorylated

S105 signal of ER-β in breast cancer cells could be due to the phosphorylaton of

other ER-β isoforms. Further studies with more breast cancer cases are needed.

It is also critcal that the phosphorylaton paterns of other ER-β isoforms are

analyzed.

P715FIXATION TIME EFFECTS ON IMMUNOHISTOCHEMICAL ASSESSMENT OF HER-2/

NEU EXPRESSION IN BREAST CARCINOMA.

S. Robertson, W. Parks. Department of Pathology, The Otawa Hospital, Otawa,

Ontario.

Objectve: Published guidelines for assessment of Her-2/neu overexpresson in

breast cancer (BC) include fxaton tme of 6 (or 8)-48 hours in neutral bufered

formalin. Weekends/holidays can make this difcult to ensure; furthermore there

is litle in the literature to support the upper limit of acceptable fxaton tme. As a

frst step in validatng an increased upper limit to fxaton tme, we investgated

efects of more prolonged fxaton tmes on imunohistochemical assessment of

Her-2/neu expression status in BC. Method: 47 cases of BC tssue were harvested,

controlling ischemic tme to <60 minutes. Samples from each specimen were fxed

in 10% neutral bufered formalin for 8, 12, 24, 72, 100, &120 hours. Samples from

each BC fxed for diferent tmes were embedded in the same block in a random

order. Her-2/neu testng of each case was thus done with all variables other than

fxaton tme held constant. IHC testng was performed on the BOND MAX

platorm using antbody SP3 (Abcam) 1/25 and H2 retrieval for 10 minutes. FISH

status for gene amplifcaton was assessed using the Vysis kit. Slide assessment

was done blindly; individual fragments were scored as 0-1 (negatve), 2+

(indeterminate) or 3+(positve) by IHC and FISH ratos of HER2/ CEP17 on 60 cells

calculated. Results: 47 cases had an adequate 24 hour sample although a full

range was not present for all specimens. The 24 hour samples included 7 at 3+, 19

at 2+ and 21 at 0-1+. None of the tssues with shorter or longer fxaton tme

showed an alteraton in IHC status and there was no drop of of % of 3+ positve

cells. FISH signals also showed no drop of in staining quality. Although all cases

were concordant across the entre fxaton range; full implicatons of longer

fxaton tme require assessment of efect on other breast predictve markers as

the same sample must be used for all testng.

P716METASTATIC, CK-7 NEGATIVE, INVASIVE LOBULAR CARCINOMA OF THE BREAST IN AN OBESE, GENOTYPIC MALE.M. Kinloch, B. Wilde Department of Pathology, St. Paul’s Hospital, Saskatoon,

Saskatchewan.

Male breast carcinomas represent approximately 1% of all diagnosed breast

cancers. Of this small percentage, less than 1% is subtyped as lobular carcinoma. It

is hypothesized that the most important risk factor for lobular carcinoma in male

breasts is exogenous or endogenous estrogen that causes a cytoarchitectual

change in the breast; but there are very few cases in the literature (~20) to show a

causal relatonship. Factors that have been associated with invasive lobular

carcinoma of the male breast include obesity, exogenous estrogen therapy and

Klinfelter’s syndrome (46XXY). The histological diagnosis of an invasive lobular

carcinoma in a male requires E-cadherin negatve staining. Our case is of a 64 year

old obese, Caucasian, male presented with a metastatc neoplasm and a query

breast primary. An ultrasound guided needle biopsy of a suspicious lef breast

mass showed malignant low grade cells, following a single-fle architecture and E-

cadherin negatvity. ER and PR stained positvely, as expected. TTF-1, PSA were

also negatve, as was CK-7. The patent did exhibit features consistent with

Klinefelter’s, but genotyping was normal. BRCA-2 testng is pending, but there is

no family history of breast cancer. This case exhibits peripheral obesity as a risk

factor for lobular carcinoma in a male and is immunohistochemically the frst

documented case in the literature of a male invasive lobular breast carcinoma to

be CK-7 negatve.

6

P717HISTOLOGIC PREDICTORS OF MALIGNANY IN BREAST CORE BIOPSIES WITH

ATYPICAL DUCTAL HYPERPLASIA.

M. Mashhour, A .Shehata , R. Saad. Department of Pathology, Sunnybrook Health

Sciences Center, Toronto, Ontario.

Background: Percutaneous core needle biopsy (CNB) is the standard technique for

histological diagnosis of breast lesions. However, a signifcant number borderline

diagnoses such as atypical ductal hyperplasia (ADH) may be challenging for the

clinicians. Previous studies have shown that a proporton of ADH (up to 30%) may

have a signifcant lesion on subsequent resecton. We studied the diagnostc

implicaton of various histologic features in breast core biopsy diagnosed as ADH

to predict malignancy in subsequent resecton. Design: We retrieved core biopsies

with ADH from the hospital archives of a large academic center from 2002 to

2010. One hundred and twenty eight cases diagnosed as ADH with their

subsequent surgical resecton were retrieved. All cases were evaluated for nuclear

grade, calcifcatons, predominant histologic architecture and size of ADH.

Histologic fndings were tabulated and correlated with the fnal diagnosis of the

resecton. Results: Out of 128 cases diagnosed as ADH, 10/128 (8%) cases

showed high nuclear grade (Grade 3), 56/128 (44%) cases as intermediate nuclear

grade (Grade 2) and 62/128 (48%) as low nuclear grade (Grade 1). The ADH size

ranges from 0.1 to 1.4 mm, with an average of 0.6+0.4 mm. Microcalcifcatons

were identfed in 54/128 (42%). Regarding the architecture patern, 44/128 (34%)

showed solid patern, 42/128 (33%) cribriform patern, 12/128 (9%)

micropapillary patern, and 30/128 (23%) were mixed patern. On resecton,

10/128 (8%) showed invasive carcinoma, 4/128 (3%) cases DCIS with

microinvasion, 32/128 (25%) cases DCIS, 17/128 (13%) ADH, 18/128 (14%) as fat

epithelial atypia and 47/128 (37%) as fbrocystc changes with ductal

hyperplasia.All cases with high nuclear grade showed malignancy on resecton (6

DCIS and 4 IDC), cases with intermediate nuclear grade showed DCIS in 18/56

(32%) and DCIS with microinvasion in 4/56 (7%), and IDC in 6/56 (11%) cases,

while cases with low nuclear grade, only 4/62 (6%) showed DCIS. There was a

signifcant correlaton between nuclear grade and detecton of malignancy in the

resecton specimen (P< 0.001). Conclusion: Our study showed associaton

between the degree of nuclear grade in ADH in core biopsy and histologic fndings

in subsequent lumpectomy. The likelihood of fnding more advanced lesions is

lower in cores with low nuclear grade. Reportng nuclear grade in pathology

report may give insight to the clinicians for appropriate management of these

patents.

P718PROGNOSTIC SIGNIFICANCE OF CD8+ T LYMPHOCYTES IN BREAST CANCER

DEPENDS UPON BOTH ESTROGEN RECEPTOR STATUS AND HISTOLOGICAL

GRADE.

J. Lachapelle1,*, K. Baker1,2,*, I. Zlobec3, T. Bismar1,4, L. Terracciano3, W.Foulkes2,4. 1Pathology, McGill University, Montreal, Quebec; 2Human Genetcs, McGill

University, Montreal, Quebec; 3Pathology, University Hospital Basel, Basel,

Switzerland; 4Oncology, McGill University, Montreal, Quebec. *These authors

contributed equally to this work.

Results of previous studies on the infuence of tumor infltratng lymphocytes on

prognosis of women with breast cancer have been mixed. This study evaluates the

role of CD8+ tumor infltratng lymphocytes as a prognostc marker in women with

breast cancer. Immunochemistry staining of CD8+ T cells was performed on a

tssue microarray of 1953 breast carcinomas. In order to select the most

discriminatng cut-of score with which to classify tumors as high or low CD8+

cell counts, ROC curve analysis was performed using the endpoint survival

(death/alive at 5 years). When all tumors were considered, no associaton

between the lymphocyte count and women survival was found. In univariate

analysis, there was a reduced disease-specifc survival for women with ER-positve

tumors with high intraepithelial lymphocyte count (p = 0.004). In those with ER-

negatve tumors, the disease-specifc survival was improved when the

intraepithelial, stromal and total lymphocyte counts were high, the total

lymphocyte count being also an independent prognostc marker on multvariate

analysis (p = 0.031). When stratfed by histological grade, on univariate analysis,

the previously observed inferior outcome in women with high lymphocyte count

and ER-positve tumors stayed signifcant only if tumors were also of low grade

and the superior outcome in those with ER-negatve tumors stayed signifcant if

tumors were also of high grade. Our results raise the possibility of diferent

immune-tumor interactons based on ER status and histological grade.

P719FIXATION TIME EFFECTS ON ESTROGEN RECEPTOR (ER) IN BREAST CARCINOMA.

S. Robertson, W. Parks. Department of Pathology, The Otawa Hospital, Otawa,

Ontario.

Objectve: Published guidelines for ER assessment of breast cancer (BC) include

fxaton tme of 6 -72 hours in neutral bufered formalin. Weekends/holidays can

make this difcult to ensure; furthermore there is litle in the literature to support

the upper limit of acceptable fxaton tme. As a frst step in validatng an

increased upper limit to fxaton tme, we investgated efects of more prolonged

fxaton tmes on ER expression in BC. Method: 67 cases of BC were harvested,

controlling ischemic tme to <60 minutes. Samples from each specimen were fxed

in 10% neutral bufered formalin for 8, 12, 24, 72, 100, &120 hours. Samples of

each BC fxed for diferent tmes were embedded in the same block in a random

order. ER testng was thus done with all variables other than fxaton tme held

constant. IHC testng was performed on the BOND MAX platorm using antbody

clone ER6F11, 1/150 and H2 retrieval for 40 minutes. Slide assessment was done

blindly; the number and intensity of cells positve in 300 cells was recorded and %

positve, H Score and Allred score calculated. Results: 67 cases had an adequate

24 hour sample although a full range was not present for all specimens. H scores

of samples fxed at 8-100 hours showed no statstcal diference compared to a 24

hour gold standard (Paired T-test). There was a statstcally signifcant decrease in

H Score from 8, 12 and 24 hours to 120 hours (p= .01, .03, .04) consistent with

some degradaton of signal with tme. This might be important if ER were used

quanttatvely. Current recommendatons do not require quanttatve scores but

use 1% as an ER positve cutof. Using this criterion 7 (10.5%) cases were negatve

in the 24 hour sample although low range positves were included (mean Hscore

167). Only 1 case with low range positvity (3.3% positve cells) at 24 hours

converted to negatve at 120 hours. Although most cases are concordant for ER

across the full fxaton range, full implicatons of longer fxaton tme require

assessment of efect on other breast predictve markers as the same sample must

be used for all testng.

P720LYMPHOEPITHELIOMA-LIKE CARCINOMA OF THE BREAST EXPRESSING CD117:

COULD GLEVIC BE USED AS A TARGETED THERAPY FOR THESE PECULIAR CASES

IN FUTURE?

M. Mashhour, R.S. Saad, W. Hanna. Department of Pathology, Sunnybrook Health

Sciences Center, Toronto, Ontario.

Case report: The patent was a 56-year old female who presented with a slowly

growing lef breast mass at the upper outer quadrant. The provisional diagnosis

was Non-Hodgkin's lymphoma, large cell type. On gross examinaton, serial

sectons revealed a large lobulated mass which occupies 80% of the lumpectomy

specimen and measures 4.0 x 3.5 x 2.0 cm. Microscopic examinaton revealed

dense nodular aggregates of lymphocytes and plasma cells interspersed and

surrounded by fat and hyalinized stroma. Germinal centers were observed in some

aggregates. High power magnifcaton showed sheets of large loosely cohesive

and highly atypical cells. These cells have pale eosinophilic cytoplasm and

moderately pleomorphic nuclei with inconspicuous nucleoli in a background of

dense lymphoplasmacytc infltraton. The lymphoplasmacytc infltraton

overshadow the epithelioid cells in some areas. There was no in situ ductal or

lobular carcinoma identfed in the specimen. These histologic features lead one

to the suspicion that this is a large B-cell lymphoma. Immunohistochemistry:

Immunohistochemical study performed using avidin-biotn-peroxidase complex

method and monoclonal antbodies against low molecular weight cytokeratn,

cytokeratn 5/6, CK7, estrogen and progesterone receptors, c-erb-2 (Her2/neu),

epidermal growth factor (Her1), CD117, B-cell marker CD20, and T-cell marker

(CD3). The stains for lymphoid markers such as CD20, CD3 were positve in the

lymphoid infltrate. Light chains Kappa and lambda were positve indicatng non-

clonal lymphocytc proliferaton. The large epithelioid cells in the center of the

lymphoplasmacytc infltrate were strongly positve for CK7 (fg.2), weak positve

staining for low molecular weight cytokeratn and high molecular weight

cytokeratn 5/6. Tumor cells were negatve for both estrogen and progesterone

receptors, Her2/neu and epidermal growth factor receptor (Her1). There was

difuse and strong positvity for CD117 (c-kit) (Fig. 3). In situ hybridizaton: In situ

hybridizaton by the ISH NIEW blue detecton kit from Ventana was used for the

detecton of EBV in tumor epithelial cells and PCR was used for the detecton of

HPV. Both tests were negatve results. Conclusion: We are reportng another case

of lymphoepithelioma-like carcinoma of the breast, which showed difuse and

strong expression for CD117 (c-kit).

7

P722ONCOTYPE DX RECURRENCE SCORES: PREDICTABLE WITH BIOMARKERS?

S.H.Bradshaw, D.H. Gravel, X. Song, E.C. Marginean, S.J. Robertson. University of

Otawa, Otawa, Ontario.

Background: Stage, grade, estrogen receptor (ER), progesterone receptor (PR) and

HER2neu status are established prognostc and predictve markers in breast

cancer. Many, but not all, low stage, lymph node (LN) negatve, ER positve

patents have a good prognosis without chemotherapy. Thus a demand exists for

predictve tools to stratfy patent risk within this subgroup. The Oncotype Dx test

is one of several mult-gene assays that atempt to fll this gap. This test produces

a recurrence score (RS) validated in prospectve clinical studies and for this reason

it is publicly funded in Ontario. The Oncotype Dx test is expensive but several

genes tested can be measured by standard immunohistochemistry (IHC). This has

led to interest in developing more cost efectve strategies to predict recurrence in

LN- ER+ patents. As several genes analyzed for Oncotype Dx RS relate to ER, PR,

HER2 & proliferatve status, it is reasonable to try to incorporate clinical-

pathological variables and these IHC scores into a predictve model. Design: A

cohort of 62 women aged 35-77 with ER +, HER2neu negatve breast cancer

completed Oncodx testng between March 2010 & February 2011. This sample

refects the populaton selected at our insttuton for Oncotype testng. The

variables investgated for inclusion in a model to predict RS score included tumor

grade, patent age, Allred ER & PR and Ki67 scores. Results: A predictve model for

Oncotype RS was developed using stepwise multple regression incorporatng

Allred ER, PR & Ki67 scores. This model accounted for 43% of the RS variability (R2

=0.43, p = 0.02). Discriminant Analysis failed to predict TailorRx categories of RS

but individually high Ki67 scores correlated with the highest (>25) TailorRx RS

category (p = 0.001). Although validaton of ideal Ki67 cut-ofs are required, this

suggests that for some cases of ER+ low stage breast cancer with high Ki67,

Oncotype DX testng may not be necessary.

P723GRANULOMATOUS MYOCARDITIS WITH CORONARY ARTERY INVOLVEMENT.

Z. Saeed Kamil , J. Butany. Department of Pathology, University Health Network,

Toronto, Ontario.

Objectves: Present a case of granulomatous myocardits with coronary artery

involvement and to discuss diferental diagnoses as well as the challenges in

diferentatng these enttes. Methods and Results: Review of UHN records

showed four cases of granulomatous myocardits (last fve years). Three were

diagnosed as sarcoidosis isolated to the heart and the fourth as granulomatous

myocardits with coronary artery involvement. This last patent is a 44 year old

man who underwent orthotopic heart transplant for giant cell myocardits,

diagnosed at endomyocardial biopsy (EMB). The explant heart showed

cardiomegaly and biventricular dilataton (marked on the lef) with, extensive,

transmural and transseptal myocardial fbrosis involving much of the heart with

chronic infammaton and numerous non-necrotzing granulomata. The coronary

arteries showed atherosclerosis and granulomata in the media, as well as in

atherosclerotc plaques. The degree of myocardial fbrosis seen is considerably

greater than one usually sees in such cases and in additon, would account for the

patent's symptoms. The lef ventricular involvement is truly striking.

Conclusions: This is the frst report of granulomatous myocardits with

involvement of the coronary arteries. The identfcaton of granulomatous

myocardits can be very difcult at EMB and highlights the need for multple

deeper sectons at biopsy. The distncton between granulomatous myocardits,

sarcoidosis and giant cell myocardits, has management implicatons and every

efort should be made to come with a defnitve conclusion, especially regarding

the etology of the patent's symptoms.

P724LEFT ATRIAL PSEUDOTUMOR CAUSED BY CASEOUS CALCIFICATION OF THE

MITRAL ANNULUS, CASE REPORT WITH REVIEW OF LITERATURE.

S. Gill MD, F. Chen, MD, PhD. Department of Pathology, Bufalo General Hospital,

The State University of New York at Bufalo, Bufalo, New York, USA.

Caseous calcifcaton of the mitral annulus (CCMA) is a rare form of periannular

calcifcaton, occurring in 0.06% of all echocardiographic studies and in 0.63% of

all patents with mitral annular calcifcaton. Here, we report a case of CCMA

manifestng as a lef atrial mass. The patent is a 78-year-old African American

female with multple co-morbidites, who presented with symptomatc coronary

artery disease and chest pain. A pre-operatve echocardiogram revealed a mass in

the posterior wall of the lef atrium which did not appear to afect the mitral valve

or protrude into the lef atrial chamber. Intra-operatvely, white toothpaste-like

material was removed from the mass lesion. Gross examinaton revealed multple

fragments of grey-white friable caseous material, measuring 3 x 2.5 x 1 cm in

aggregate. Bacterial and fungal cultures from this material were both negatve.

Microscopic examinaton showed this material to be amorphous, non-viable,

basophilic, and acellular with foci of calcifcaton. These morphological features

were diagnostc for CCMA. Review of the literature indicated that CCMA is a very

rare benign lesion, presentng as a round, tumor-like mass with central

echolucencies on echocardiography. We believe our case report will further raise

the awareness of CCMA so that pathologists and radiologists can get familiar with

this rare disease to avoid potental misdiagnosis.

P725MITOCHONDRIAL DNA DEPLETION SYNDROME AN UNUSUAL REASON FOR

INTERSTAGE ATTRITION AFTER THE MODIFIED STAGE1 NORWOOD OPERATION.

W. Bahitham 1 , D. Cave2, D.B. Ross MD, FRCS(C)3, C. Sergi MD, PhD1, I. Adata

MBChB, FRCP(C)4. Department of 1Laboratory Medicine and Pathology,

Departments of 2Anesthesia and Pediatrics, 3Cardiac Surgery,4Pediatrics, Stollery

Children’s Hospital, Mazankowski Insttute, University of Alberta, Edmonton,

Alberta.

Introducton: Mitochondrial DNA depleton syndromes are clinically

heterogeneous disorders characterized by a severe quanttatve reducton of total

mitochondrial DNA. We report here, for the frst tme to the best of our

knowledge, a patent afected with mitochondrial DNA depleton syndrome and a

variant of hypoplastc lef heart syndrome who died 16 weeks afer a modifed

stage 1 Norwood. Case presentaton: A term baby weighing 3.6 kg was delivered

by Caesarean secton. A prostaglandin E 1 infusion was started in the delivery

room because a prenatal ultrasound had demonstrated a duct dependent

systemic circulaton with small lef heart structures. A postnatal echocardiogram

diagnosed a variant of the hypoplastc lef heart syndrome with a large muscular

ventricular septal defect. The aortc valve and mitral valve annulus measured 3

and 4 mm respectvely. The lef ventricle from mitral annulus to apex measured

1.4 versus 3.1 cm for the right ventricle from tricuspid annulus to apex. There was

an aortc coarctaton with an unrestrictve patent ductus arteriosus and atrial

septal defect. Bilateral superior vena cavae were present, with the lef draining to

the coronary sinus.Chromosome analysis revealed a 46, XY karyotype. Neonatal

metabolic screen, liver functon tests and INR were normal. Conclusion:

Interstage mortality afer the Norwood stage 1 remains a serious problem and

should be considered in the congenital disorders of the outlow tract of the heart.

P726CYTOLOGY IMMUNOMARKER VALIDATION STUDY: A COMPARISON AND

EVALUATION WITH IMMUNOHISTOLOGY.

A. Shibani, E. Tugaleva, B. Wehrli, M.M. Weir. Dept. of Pathology, London Health

Sciences Centre & University of Western Ontario, London, Ontario.

Background: Immunochemistry (IC) is a useful ancillary tool for the interpretaton

of cytologic samples. The cell block (CB) rather than a ThinPrep (TP) sample is

usually used. In the literature, there are few studies comparing IC on TP, CB and

histologic (H) samples. Purpose: To validate cytology IC by comparing: 1) TP & CB

routne patent samples; and 2) TP, CB and H optmally prepared samples.

Methods: 1) 23 TP & CB preparatons from routne patent samples (13 fuids, 2

lymph nodes, 8 respiratory exfoliatves) were stained with 9 IC markers:

CD5,CD20,CD45,CD68, CK7, BerEP4, B72.1, MOC-31 & TTF-1. 2). Fresh tssue from

10 tonsils, 4 lungs, & 3 colon carcinomas was obtained for TP, CB & H preparatons

to which, in additon to the IC markers used in part 1, seven additonal markers

were applied: CD3, CD10, CD23, CK20, CKCAM5.2, CKAE1/3, and CDX2. IC was

performed either manually or using the Ventana BenchMarkXT system. IC slides

were reviewed by two authors for intensity (INT 0-3+), % cell distributon (CD 0-

4+) and Q score (additon of INT & CD). An immunomarker was considered

validated when the Q score was 5 or higher, in > 75% of cases, and had a Q score

variaton within 2 points. Results: On routne patent samples: CK7 & CD68

validated on TP & CB; MOC-31 validated only on TP; all other markers were not

validated (CD5, CD20 & CD45, TTF-1, BerEP4, B72.3). On optmally prepared

samples: CD45, CD5, CD68, CK 7,CK20, CKCAM5.2 & CKAE1/3 validated on TP, CB

& H; BerEP4 & B72.3 did not validate on any preparaton;

CD3,CD10,CD20,CD23,MOC31, CDX2, & TTF-1 validated only on H. Conclusions:

Routne patent samples had fewer validated samples (33%) than optmally

prepared samples (44%). Rare markers could not be validated on TP, CB or H.

Revalidaton of some IC markers is merited at our insttuton.

8

P727REDUCED CENTRIFUGATION TIME CONSERVES LABORATORY RESOURCES, WHILE

IMPROVING DIAGNOSTIC UTILITY IN SOME SAMPLES.

A. Adamiak1, S. MacDonald1, and S. Boerner1,2. 1Laboratory Medicine Program,

University Health Network and the 2University of Toronto, Toronto Ontario.

Background: Certain non-gynecologic cytology (NGC) specimens require

centrifugaton prior to ThinPrep slide producton, however, the optmum duraton

of centrifugaton has not been established. AIM: To determine the efect of

reducing centrifugaton tme from 5 minutes to 1 minute on the diagnostc and

adequacy rates of NGC specimens undergoing ThinPrep slide producton.

Methods: Diagnostc and adequacy rates were compared for samples from an 18

month period following reducton of centrifugaton tmes from 5 minutes to 1

minute, to those rates from the 3 years preceding the change. Specimen types

included Bronchial (washings and brushes), Body cavity fuids (pleural fuid,

peritoneal fuid, pericardial fuid, peritoneal washings) and Urine (voided and

bladder washings). Results: There was an increase in the detecton of abnormal

cells in Urines (1 min = 12.1%, 5 min = 10.1%, p<0.0001). There was a decrease in

unsatsfactory rates for Urines (1 min = 3.3%, 5 min= 3.9%, p<0.0223). There were

no statstcal diferences in detecton of abnormal cells or in the adequacy rates

for Bronchial or Body cavity fuid specimens. Conclusion: Shortening

centrifugaton tmes during processing of NGC specimens that undergo ThinPrep

slide producton increases the detecton of abnormal cells, while decreasing the

rate of unsatsfactory cases in Urines. In the majority of specimens however,

there is no signifcant diference in diagnostc rates, and therefore a reducton of

the duraton of centrifugaton expedites processing of samples and conserves

laboratory resources, without compromising diagnostc utlity.

P728ENDOSCOPIC ULTRASOUND GUIDED FNA OF POSTERIOR MEDIASTINAL LESIONS:

CYTOPATHOLOGY ASPECT.

V. Zherebitskiy 1 , M. Cantor2, P. Baker1, E. Ravinsky1. 1Department of Pathology and 2Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba.

Objectve: Tissue sampling with pathologic diagnosis is an important component

of the diagnostc work up of mediastnal lesions. Since 1993 transesophageal

endoscopic ultrasound guided fne needle aspiraton (EUS FNA) has been used for

lesions involving the posterior mediastnum. EUS FNA became available in

Manitoba in 2005. Since that tme EUS FNA of mediastnal lesions has been used

for confrmaton and staging of malignancies, predominantly lung cancers. The

goal of this study was to assess yield and diagnostc accuracy of EUS FNA as well

as its infuence on management of patents with posterior mediastnal lesions.

Methods: All EUS FNAs were performed by single physician, using an Olympus

curvilinear array echoendoscope (GF-UC140P, Olympus, Canada) equipped by 22

gauge FNA needle (NA-200H-8022, Olympus Canada). Rapid on-site evaluaton of

the aspirate by a cytotechnologist using the Quick-Dif stain was performed. The

diagnosis was rendered by a cytopathologist using Quick-Dif and PAP stained

smears and H & E stained cell blocks. Special stains and immunohistochemistry

were performed on the cell blocks. Patents with primary esophageal lesions were

excluded from the study. Surgical and clinical follow up were sought in all cases.

Results: 35 out of 47 patents who underwent mediastnal EUS FNA during 2005-

2009 were chosen for the study. All of them had suspicious radiologic fndings.

When performed bronchoscopy or mediastnoscopy had failed to yield diagnostc

material. Diagnostc yield of EUS FNAs was high (89%) confrming malignancy in

61%. Squamous cell carcinoma was the most prevalent malignant tumour

following by small cell carcinoma and poorly diferentated adenocarcinoma.

Where surgical pathology was available, there was 100% concordance with FNA

diagnosis. FNA had impact on management in 89% of cases. Conclusion: EUS FNA

is efectve in the assessment of posterior mediastnal lesions and requires close

cooperaton of endoscopist and cytopathologist.

P729A RATIONALE FOR THYROID FINE NEEDLE ASPIRATION ADEQUACY CRITERIA.

M. Bonert1, S.L. Boerner1,2. 1Department of Laboratory Medicine and Pathobiology,

University of Toronto; 2Department of Pathology, University Health Network,

Toronto, Ontario.

Background: Criteria for adequacy of thyroid fne needle aspirates (FNAs) remains

debated, with epithelial quanttaton gaining acceptance. However, there is litle

evidence upon which to base a minimum number of epithelial cells necessary to

establish adequacy. Objectve: Develop adequacy criteria, using epithelial

quanttaton, for thyroid FNAs using a specifc, reproducible histomorphological

feature and probability. Methods: The frequencies of the diagnostc features of

the most common well-diferentated thyroid malignancy, papillary thyroid

carcinoma (PTC), were determined by a literature search. Probability was then

used to calculate the theoretcal non-sample rate with diferent sample sizes using

the frequency data. Results: The least frequent, yet highly predictve feature of

papillary carcinoma is cytoplasmic intranuclear pseudoinclusions, which are

present at an approximate rate of 1 of 77 cells in conventonal papillary

carcinoma. Thus, a sample of at least 229 lesional cells is required to have a

sensitvity of greater than or equal to 95% for the detecton of papillary

carcinoma, assuming that the presence of a single intranuclear pseudoinclusion

can be detected when lesional tssue is a sampled. The non-sample rate for

features with low frequencies approximates an exponental decay curve that is

dependent on the sample size (s) divided by the frequency (f). To obtain a 95%

probability of sampling two pseudoinclusions and three pseudoinclusions

(assuming f=77) requires 363 cells and 483 cells respectvely. Conclusions:

Probability provides a ratonal approach for establishing thyroid FNA adequacy

criteria. A sample of 400 follicular cells should consttute a minimum for thyroid

FNAs, such that several pseudoinclusions are likely sampled within a PTC.

Probabilistc approaches and histomorphologic data may be useful to guide

establishment of adequacy criteria for other types of pathology specimens.

P731PATTERN OF INTESTINAL MUCOSAL INJURY RESEMBLING CHEMOTHERAPY

CHANGES IN A PATIENT TAKING CHINESE HERBAL MEDICATION ENEMAS.

B. Mitrovic 1 , A. Newman2, R. Riddell1. 1Department of Pathology and Laboratory

Medicine, Mount Sinai Hospital, Toronto, Ontario; 2Department of Medicine,

Mount Sinai Hospital, Toronto, Ontario.

We present a 19 year old woman with colonic mucosal injury associated with

Chinese herbal medicaton enemas. She presented to another insttuton in early

2009 with abdominal pain and diarrhea; based on clinical, endoscopic and

histopathologic fndings a diagnosis of infammatory bowel disease was rendered.

She was treated with steroids and Salofalk enemas, but was noncompliant with

her medicatons, and atempted to treat her symptoms with various Chinese

herbal medicatons, including enemas. She was seen at our insttuton in 2010.

Colonoscopy again showed severe colits in the rectum and distal sigmoid colon.

Biopsies taken at the tme showed regeneratng crypts at diferent stages of repair

with a dense eosinophilic infltrate in the lamina propria. The appearance was

strikingly similar to the patern of mucosal injury seen in patents receiving

chemotherapy. Review of a previous set of biopsies taken in 2009 demonstrated

similar histological changes. This patern of injury was felt to be incompatble with

IBD and was atributed to her use of Chinese herbal medicatons. Given the distal

distributon of disease, it is hypothesized that the herbal enemas may be the

culprit. The patent was urged to discontnue these Chinese remedies, and, at the

tme of this writng, she remains asymptomatc. This patent illustrates the

potentally toxic efects of herbal medicatons on gastrointestnal mucosa, and is

the frst report of this distnctve patern of colonic mucosal injury in a patent

using herbal medicatons. The potental for mucosal injury secondary to herbal

medicatons should be considered in patents with “colits”.

P732MULTIFOCAL ADENOCARCINOMA OF A NEOBLADDER IN A PATIENT WITH LYNCH

SYNDROME: CASE REPORT AND REVIEW OF THE LITERATURE.

B. Mitrovic 1 , S. Skeldon2, A. Zlota2, R. Kirsch1. 1Department of Pathology and

Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario; 2Department of

Surgery, Mount Sinai Hospital, Toronto, Ontario.

Neoplasms arising from orthotopic neobladder mucosa are rare, with only a few

cases reported in the literature. We present the case of a 53 year old man with

Lynch syndrome who developed a multfocal neobladder adenocarcinoma 13

years afer undergoing a pelvic exenteraton with cystectomy and orthotopic

neobladder constructon for advanced rectal cancer. The patent presented with

gross hematuria. An exophytc lesion was seen at cystoscopy. Biopsies showed an

adenocarcinoma with difuse immunoreactvity for CDX2, and patchy

immunoreactvity for CK7 and CK20. Immunohistochemistry for DNA mismatch

repair proteins (hMLH1, hMSH2, hMSH6, and hPMS2) showed absent nuclear

staining for MSH2 and MSH6. The patent subsequently underwent resecton of

the neobladder. Two separate exophytc lesions were seen arising from the

mucosa; both tumours showed features typical of microsatellite unstable

adenocarcinoma, with a broad invasive front, intratumoral and peritumoral

lymphocytes, and poor diferentaton in one of the tumours. Foci of dysplasia

were identfed in the surrounding mucosa. Extrapolatng from the American Joint

Commitee Cancer Staging Manual, 7th editon for small bowel carcinoma, the

pathological stage was pT4NxMx. To our knowledge, this is the frst case report of

a neobladder carcinoma in a patent with Lynch syndrome, and also the frst

report of a multfocal neobladder adenocarcinoma. While the risk of carcinomas

arising in orthotopic neobladders is extremely low, the risk in patents with Lynch

syndrome may be substantally higher given the underlying DNA mismatch repair

9

defect. If neobladder creaton is undertaken, these patents should be closely

monitored for the development of secondary malignancy.

P733MUCIN PROFILE IN GOBLET CELL CARCINOID OF THE APPENDIX.

F.Siadat, S. Bradshaw, M. Gomes, E. Marginean, K. Mai, B. Nguyen. Pathology and

Laboratory Medicine, University of Otawa, Otawa, Ontario.

Goblet cell carcinoid (GCC) of the appendix is a mixed exocrine-endocrine tumor.

Unlike adenocarcinoma (ADC) and signet ring cell carcinoma (SRCC) of the colon,

the mucin profle of GCC has not been characterized. The objectve of this study is

to identfy the mucin profle of GCC. Methods: 10 cases of GCC (6 men, 4 women,

median age 59), 5 cases of colonic SRCC and 5 cases of colonic ADC (5 men, 5

women, median age 68) were retrieved from our Pathology archives. Tissue

sectons were immunostained with antbodies against MUC1, MUC2, MUC5AC

(MUC5). Immunostaining for chromogranin A, synaptophysin, NSE, CD56 and MIB-

1 were also done on GCC cases and confrmed an endocrine component.

Cytoplasmic staining was scored based on proporton of positve tumor cells as

follows: - (less 5%), 1 + (5-25%), 2+ (26-50%), and 3+ (>50%). Results: All GCC and

SRCC were MUC1 negatve and MUC2 3+. In GCC group, MUC5 was 2-3+ in 4 cases

and negatve in 6 cases. In SRCC group, MUC5 showed 3+ reactvity in all cases and

was 1-2+ in 3/5 cases. All ADC cases were MUC1 1-2+, MUC2 3+ and 2/5 ADC

cases were MUC5 2+. Conclusions: 1) This study is the frst to report the following

mucin profle of GCC: MUC1-/MUC2+/MUC5 variably expressed; 2) The above

MUC markers are similarly expressed in GCC and SRCC thus cannot be used to

distnguish these enttes in tumors with ambiguous morphology. These

preliminary fndings will need further assessment and confrmaton in larger

series.

P734TWO CASES OF RESIDUAL ABNORMAL INNERAVTION AFTER ENDORECTAL PULL

THORUGH FOR HIRSCHSPRUNG DISEASE: A CAUTIONARY TALE.

D. Grynspan1, J. de Nanassy1, W.A. Staines2, M. Betolli3. 1Department of

Pathology, Children’s Hospital of Eastern Ontario and University of Otawa; 2Department of Cellular and Molecular Medicine, University of Otawa; 3Pediatric

Surgery, Children’s Hospital of Eastern Ontario and University of Otawa, Otawa,

Ontario.

Introducton: Intraoperatve seromuscular biopsies are widely submited for

quick-secton in the surgical management of Hirschsprung disease. These are

performed to help determine where the aganglionic segment ends and normal

innervaton begins. Cases: In the frst case the intraoperatve frozen secton

biopsy was interpreted as showing normal ganglion cells. On permanent secton

examinaton of the excised specimen it was noted that there were also

hypertrophic nerves, suggestng the colon had been transected within the

transiton zone. The original frozen secton slides were reviewed and some

possible hypertrophic nerves were in retrospect acknowledged. In the second

case the intra-operatve seromuscular biopsy showed ganglion cells and no

defnite hypertrophic nerves and this impression was upheld on examinaton of

permanent sectons of the same material. Nonetheless the proximal resecton

margin of the excised specimen showed an uneven circumference with some parts

having ganglion cells and other parts being aganglionic. Discussion: These cases

highlight potental limitatons of the use of the seromuscular biopsy for

intraoperatve consultaton . Hypertrophic nerves may be difcult to recognize

using the frozen secton technique. This problem may be overcome with increased

diagnostc experience or with the use of ancillary techniques that can be

performed within a tme frame acceptable for frozen sectons. The potental

inherent unreliability of a biopsy from a single site along the circumference will

also be explored in light of a conceptual model of the transiton zone based on

current knowledge. New approaches such as intra-operatve quick secton

examinaton of the entre proximal resecton margin (“donut”) will be discussed.

P735FIRST CASE REPORT OF SYNCHRONOUS GASTRIC AND APPENDICEAL

CARCINOMA PRIMARIES IN CDH1-ASSOCIATED HEREDITARY DIFFUSE GASTRIC

CANCER.

L. Hamilton1, K. Jones2, N.Church2, S. Medlicot1. 1Dept of Pathology and

Laboratory Medicine, 2Dept of Surgery, University of Calgary, Calgary, Alberta.

Objectve: Hereditary difuse gastric cancer (HDGC) is an inherited cancer

syndrome in which individuals develop difuse gastric carcinoma at a young age;

approximately 40% of cases are associated with E-cadherin (CDH1) gene

mutatons. As a hereditary cancer syndrome, multple organ sites can be involved

besides stomach, and various malignancies have been reported with HDGC,

primarily lobular carcinoma of the breast. Although an associaton with colonic

carcinoma has been documented, primary appendiceal carcinoma occurring with

CDH1-associated HDGC has not previously been reported in the English literature.

Methods: A case report of a primary appendiceal carcinoma arising in an

individual with CDH1-associated HDGC. Results: A 51-year old woman, identfed

as a CDH1 mutaton carrier, underwent prophylactc gastrectomy, as well as

interval appendectomy for a history of acute appendicits one-month prior to

surgery. Pathologic evaluaton of the gastrectomy specimen revealed multfocal

poorly diferentated difuse-type adenocarcinoma, confned to the lamina propria

(intramucosal). Within the appendix, a high-grade signet ring cell carcinoma with

mucinous features was identfed. By immunohistochemistry, the gastric

carcinoma was CK7+, CK20+, CDX2- and weakly E-cadherin+ (upper

gastrointestnal phenotype), and the appendiceal carcinoma was CK7-, CK20+,

CDX2+ and E-cadherin+ (colorectal phenotype). Conclusions: To the best of our

knowledge, this is the frst case report of synchronous primary difuse-type gastric

cancer and primary appendiceal carcinoma arising in CDH1-associated HDGC. If

symptoms atributable to the lower gastrointestnal system exist in these

individuals at risk for malignancy at multple organ sites, consideraton should be

given for colonoscopy prior to prophylactc gastrectomy to provide more defnitve

surgical management.

P736MICROSATELLITE INSTABILITY STATUS DOES NOT PREDICT ABSOLUTE LYMPH

NODE OR NEGATIVE LYMPH NODE RETRIEVAL IN STAGE III COLORECTAL CANCER.

E. MacQuarrie 1 , T. Arnason1, J. Gruchy1, S.R. Yan1, B. Nassar1, A. Drucker2, W.Y.

Huang1. 1Department of Pathology, QEII Health Sciences Center, Halifax, Nova

Scota; 2Department of Medicine, QEII Health Sciences Center, Halifax, Nova

Scota.

The correlaton between a high absolute lymph node (LN) resecton number in

colorectal cancer (CRC) resecton specimens and improved overall survival is well

known. A recent prospectve study describes an associaton between a high rate of

microsatellite instability (MSI-H) and a high absolute LN count in AJCC stages I and

II CRC. The authors suggest that a high numbers of LNs may be predictve of MSI-H

status in that cohort. Our objectve is to determine whether these associatons

can be applied to an isolated cohort of AJCC stage III CRC. Reports from 123 stage

III CRC resecton specimens from January 1995 – January 2006 were reviewed.

Expression of the DNA mismatch repair (MMR) proteins was determined by

immunohistochemistry on archived tssue and confrmed by polymerase chain

reacton. The mean absolute LN count in MSI-H vs. MSS tumors (14.5 vs. 14.6,

p=0.976) and the mean number of negatve LNs in MSI-H vs. MSS tumors (11.2 vs.

11.4, p=0.928) were not signifcantly diferent. Within our cohort of 123 tumors,

the median absolute LN harvest was 12 and the median negatve LN count was 10.

We found no signifcant diference between MSS and MSI-H absolute LN counts

(p=0.605) or negatve LN counts (p=0.795) when analyzed with respect to

percentage of cases above and below the medians. Our retrospectve study of a

cohort of stage III CRC does not identfy a signifcant relatonship between MSI-H

status and a higher absolute number of LNs retrieved. We did not fnd any

associaton between MSI-H status and number of negatve LNs. This raises the

possibility that while these associatons may be seen in stage I and II CRC, they do

not hold true in stage III CRC.

P737ICILIN ATTENUATES TRI-NITRO-BENZENE SULPHONIC ACID INDUCED COLITIS IN

MICE.

L. Zhao1, E. Hyun2, M.D. Hollenberg2, R. Ramachandran2. 1Department of

Pathology, University of Calgary, Alberta; 2Department of Physiology and

Pharmacology, University of Calgary, Alberta.

Aims: Cold temperatures are commonly used as a local ant-infammatory

treatment. TRPM8 and TRPA1 are the members of the transient receptor potental

family of ion channels and play an important role in detectng mild and noxious

cold temperatures respectvely. TRPA1 is actvated by cold temperatures below

18°C and TRPM8 is reported to be actvated at temperatures below 25°C. These

channels are also actvated by chemicals such as menthol and icilin. It is well

established that tri-nitro-benzene sulphonic acid (TNBS) can induce colits in mice,

with clinical and histopathological fndings resembling those seen in human

Crohn’s disease. We hypothesised that the super-cooling agent icilin would

diminish TNBS induced colits in mice by mimicking the protectve efects of cold

temperatures. Methods: Colonic infammaton in C57BL6 mice was induced by

treatment with tri-nitro-benzene sulphonic acid (TNBS, 2mg in 100µ l of 40%

ethanol, intracolonically). Colits was allowed to develop for 7 days and icilin

(5mg/kg in 3% DMSO/saline, intraperitoneally) was administered daily. Control

animals received icilin but were not treated with TNBS. Seven days afer inducton

of colits, macroscopic damage score and bowel thickness were evaluated.

Results: Mice treated with icilin alone showed no symptoms of colits as well as no

morphological evidence of infammatory bowel disease. Mice treated with TNBS

10

presented with weight loss and bloody diarrhea consistent with development of

colits. Large bowel from these mice revealed marked architectural damage,

infammatory infltrate and increases in bowel thickness. In contrast, TNBS-

induced clinical disease parameters and histological damage scores were

signifcantly reduced in mice that received daily icilin treatment. Conclusion: We

conclude that icilin atenuates infammaton associated with the development of

colits in mice. Agents that can actvate TRPM8/TRPA1 channels may represent

novel therapeutcs for colits. A beter understanding of the ant-infammatory

signalling actvated by the cold-sensitve channels will uncover novel therapeutc

strategies for managing infammatory bowel disease.

P738MORPHOLOGICAL SPECTRUM OF BENIGN EPITHELIAL INCLUSIONS IN THE

PERIPANCREATIC LYMPH NODES: A REPORT OF TWO CASES SUGGESTING A

RELATIONSHIP TO PANCREATIC LYMPHOEPITHELIAL CYSTS.

Z. Zheng1, M. Molinari2, R. Gupta1, H. Sapp1, I. Wanless1 and W.Y. Huang1. 1Department of Pathology, 2Department of Surgery, Queen Elizabeth II Health

Sciences Centre, Dalhousie University, Halifax, Nova Scota.

Benign epithelial inclusions are rarely found in peripancreatc lymph nodes. We

described two cases of benign epithelial inclusions in the peripancreatc lymph

nodes with detailed discussion of diferental diagnosis. The frst case was a 2.2

cm lymph node from a 51-year-old woman with pancreatc ductal

adenocarcinoma. The second case was a 4.3 cm lymph node from a 28-year-old

man with a cholangiocarcinoma of the distal common bile duct. The epithelial

inclusions in the frst case consisted of several small squamous cell nests with

central duct-like lumina. The lymph node from the second case showed

convoluted cystc inclusions lined by a single layer of bland cuboidal epithelium

with scatered mucin-producing cells. We conducted a literature review on similar

lesions and found that some of lesions were associated with pancreatc

heterotopia. It is imperatve in clinical practce to distnguish these epithelial

inclusions in the lymph nodes from tumor metastasis. A hypothetc connecton of

these benign epithelial inclusions in the peripancreatc lymph nodes to the

enigmatc pancreatc lymphoepithelial cysts was suggested.

P739LARGE CELL NEUROENDOCRINE CARCINOMA ARISING IN A SESSILE SERRATED

ADENOMA: A NOVEL OBSERVATION.

K. Naert1, M.P. Dupre1. 1Department of Pathology and Lab Medicine, Calgary Lab

Services and University of Calgary, Calgary, Alberta.

Sessile serrated adenomas (SSAs) have been shown to be precursors to colorectal

cancer by the microsatellite instability pathway. Specifc cancer morphologies and

histologic features have been associated with precursor SSAs. A 68-year-woman

underwent polypectomy of two right-sided colonic polyps identfed during

routne screening colonoscopy. Both of the lesions were histologically identfed as

sessile serrated adenomas (SSAs). The larger of the two was found to harbour a 2

mm invasive tumor composed of large cells arranged in nests and cords. Tumor

cells were of high nuclear grade. Tumoral mucin was not identfed. Tumor cells

were positve for synaptophysin, cdx-2, and cytokeratns 7 and 20. Calretnin

staining was negatve and both the invasive carcinoma and the associated SSA

showed decreased expression for hMLH-1 compared to normal control tssues. A

diagnosis of large cell neuroendocrine carcinoma arising in an SSA was rendered.

Colonoscopic perforaton lead to a segmental resecton in which no residual

tumor or lymph node metastasis could be identfed. To date, medullary,

mucinous, serrated, and signet ring carcinomas have been reported in associaton

with SSAs. Other features common to these cancers include tumor-infltratng

lymphocytes, Crohn’s-like lymphoid aggregates, locaton in the right colon,

occurrence in older women, and an overall beter prognosis than conventonal

colorectal cancers. Large cell neuroendocrine carcinoma has not yet been

reported in associaton with SSAs, with this case suggestng a rare but potentally

novel end-point for the microsatellite instability pathway. It remains to be seen

whether tumors of this nature will have the beter prognosis associated with SSA-

derived cancers, or the poorer prognosis of large cell neuroendocrine carcinomas

of the colon.

P740PROGRESSION IN THE HISTOLOGICAL FINDINGS IN A RAT MODEL OF DIET

INDUCED NON ALCOHOLIC FATTY LIVER DISEASE.

A.C. Don-Wauchope 1 , H. El-Zimaity2, A.C. Holloway3. 1Departments of Pathology

and Molecular Medicine and Medicine, McMaster University, Hamilton, Ontario; 2Department of Laboratory Medicine and Pathobiology, University of Toronto,

Toronto, Ontario; 3Department of Obstetrics and Gynaecology, McMaster

University, Hamilton, Ontario.

Introducton: Faty Liver is an increasing health problem as the increasing

incidence is associated with the rise of obesity. Faty liver is now understood to be

one of the main contributng factors to cryptogenic cirrhosis of the liver. The

understanding of the early development of faty liver is limited as many animal

and human studies have focussed on the progression of fbrosis. We designed a

study to investgate the early development of faty liver from a high fat diet in

Wistar Rats. Methods: Nulliparous Wistar rats (N=10) were mated and allowed to

deliver normally. Liters were culled to 12 retaining 6 male and 6 female pups. At

weaning (postnatal day 21), male and female pups from each liter were randomly

assigned to a control diet or high fat diet (3 pups of each gender per diet). At 7, 26

and 39 weeks of age, two male and two female pups from each liter, one from

each diet group were randomly selected for necropsy. Histology was assessed by

the Brunt scoring system. Results: By 7 weeks of age, rats fed the high fat diet

were signifcantly heavier than their siblings on the control diet. There were

diferences in fat score, fat type and distributon in the livers of high-fat fed rats;

an efect which was evident by 7 weeks of age in female rats but not untl 26

weeks of age in male rats. The distributon and nature of faty change in the liver

showed gender specifcity at all tme frames. There was no signifcant

infammaton detected. Discussion/Conclusion: The early introducton of a high

fat diet has resulted in the development of histological changes consistent with

faty liver from 4 weeks afer the introducton of the high fat diet. There were

signifcant gender diferences in the onset and progression of faty liver, which

require further study to develop understanding of the early changes in faty liver

disease.

P741EXPRESSION OF E-CADHERIN AND Β-CATENIN IN TWO CHOLANGIOCARCINOMA

CELL LINES (OZ AND HUCCT1).

Y. Abuetabh1, S. Persad2, S. Nagamori3, J. Huggins4, R. Al-Bahrani1, C. Sergi1. 1Department of Lab. Medicine and Pathology, University of Alberta Hospital,

Edmonton, Alberta; 2Department of Pediatrics, University of Alberta Hospital,

Edmonton, Alberta 3Department of Virology II, Natonal Insttute of Infectous

Diseases, Japan; 4Provincial Lab, Canada.

Background: Cholangiocarcinoma (CC) is the most frequent malignant epithelial

tumor of the biliary system. CC has received an increasing interest due to its

diferent etologic factors, invasiveness, and difculty of diagnosis at early stage.

Calcium-dependent adherence proteins or cadherins are a family of proteins

essental to connect the plasma membrane of adjacent cells. Linkage of cadherins

with the cytoskeleton occurs through another class of proteins, called catenins. E-

cadherin forms a mutually exclusive complex or unit with β-catenin. Loss of E-

cadherin - β-catenin adhesion represents an important step in the progression of

many epithelial malignancies. Our aim was to investgate the expression and

localizaton of E-cadherin and β-catenin in two CC cell lines. Materials and

Methods: OZ and HuCCT1 cells represent homogeneous, functonal human biliary

epithelial tumor cell lines. Western blot analysis, immunofuorescence and

confocal laser microscopy were used to identfy the protein expression and their

cyto-localizaton and co-localizaton. Results: Both CC cell lines expressed E-

cadherin and β-catenin, but they remarkably showed diferent localizaton

paterns. In HuCCT1, both E-cadherin and β-catenin were localized in the

cytoplasm, while in OZ these proteins were localized in the cytoplasmic

membrane only. Conclusion: To the best of our knowledge, this is the frst tme

that E-cadherin and β-catenin have been studied in detail in these two cell lines

and these data seem to be very promising, because they can add more insights

into the cell biology of CC.

P742DOES SIRT1 HAVE PLEIOTROPIC EFFECTS DURING CANCER DEVELOPMENT OF

THE LIVER?

R. Albahrani1, D. Tuertscher2, R.J. Abdualmjid1, Y. Abuetabh1, C. Sergi1. 1Department of Lab. Medicine and Pathology, University of Alberta Hospital,

Edmonton, Alberta; 2Insttute of Pathology, Medical University of Innsbruck,

Austria.

Background: Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are

the major adult liver cancers. Although some phenotypic overlap is known, both

tumors have usually diferent histology and prognosis. Gene expression and

deacetylase actvity of the class III histone deacetylase SIRT1 are up-regulated in

cancer cells due to oncogene overexpression or loss of functon of tumor

suppressor genes. SIRT1 may play a critcal role in tumor initaton, progression,

and drug resistance by blocking senescence and apoptosis, and promotng cell

growth and angiogenesis. Pleiotropic efects (ant-proliferaton and ant-apoptotc)

have been indicated during colorectal cancer development. Our aim was to

investgate the expression of SIRT1 in liver malignancies. Materials and Methods:

We investgated 18 malignant tumors of the liver, including 12 HCC and 6 CC by

11

immunohistochemistry using a monoclonal antbody against SIRT1. Results: We

found an expression of SIRT 1 in 7 out of 12 HCC and in 4 out of 6 CC. Conclusions:

These inital results including clinical pathological correlaton seem to be in line

with colorectal cancer data showing some SIRT1 overexpression in liver

malignancy. SIRT is probably unsuitable for diagnostc purposes, but it may have

pleiotropic efects during cancer development in the liver.

P743TUMOR BUDDING IN STAGE IIA COLORECTAL CARCINOMA: SEMI-QUANTITATIVE

ASSESSMENT.

M. Caragea, J. Sy, J.R. Parft, D.K. Driman. Department of Pathology, LHSC,

University of Western Ontario, London, Ontario.

Objectve: Tumor budding (TB) in colorectal carcinoma (CRC) refers to single or

clusters of tumor cells at the tumor’s invasive front; it is an adverse prognostc

factor. Our aim was to develop a reproducible method for assessing TB and to

assess its prognostc signifcance. Methods: 73 cases of stage IIA or less CRC with

at least 5 yrs follow up and no recurrence, neoadjuvant therapy, infammatory

bowel disease or polyposis syndromes studied. Overall survival (OS) tme, local

recurrence, metastasis and adjuvant therapy were recorded. TB defned as a single

cell or cluster of ≤4 tumor cells at the invasive front. Slides evaluated by two

observers; those with TB seen at 4X were re-evaluated at 20X and categorized as

low-grade (<10 buds/feld) (LGTB) or high-grade (≥10 buds/feld) (HGTB). Absolute

TB counts were performed. The semi-quanttatve method was compared with

absolute counts and between observers. Discrepant cases were re-assessed to

achieve consensus. OS analyzed by Cox regression. Results: 69 cases = low grade,

55 cases = T3N0, 17 cases = T2N0, 1 case = T1N0. Three patents had local

recurrence; 9 had distant metastases, 23 deaths (8 due to CRC). 68 cases = TB-

positve, 5 = TB-negatve. 60 cases = LGTB; 8 = HGTB. There was no statstcally

signifcant diference in OS between positve and negatve cases or between LGTB

and HGTB; HGTB cases trended towards a higher risk of death (HR=2.512). There

was good-excellent interobserver agreement at 4X (K=0.53) and 20X (K=0.79), as

well as with absolute counts (K=0.92). The semi-quanttatve method strongly

correlated with the absolute counts (K=0.79). Conclusion: TB assessment using a

semi-quanttatve method correlates with absolute TB counts with good

interobserver agreement. Patents with HGTB showed a trend towards a higher

risk of adverse events.

P744PROSTATIC MUCINOUS ADENOCARCINOMA IN A PATIENT WITH HISTORY OF

COLONIC MUCINOUS ADENOCARCINOMA: THE HELPFUL CLUES.

D. El Demellawy1,2, S. Tauqir3, S. Alowami3. Pathology Departments: 1Northern

Ontario School of Medicine, Sudbury, Ontario; 2William Osler Health Center,

Brampton, Ontario; 3McMaster University, Hamilton, Ontario.

Mucin producing adenocarcinomas of the prostate are rare. We present a 73 year

old man presented with elevated PSA and free to total rato of less than 0.04. His

had a signifcant history of mucinous colonic adenocarcinoma, NOS (pT2, pN0,

pM0), treated 5 years prior with right hemicolectomy. Transrectal ultrasound

guided biopsy revealed prostatc adenocarcinomas. A radical prostatectomy

revealed mucinous adenocarcinomas with dissectng mucin lakes containing

foatng islands of tubuloacinar glands. The malignant glands and mucin infltrated

fbromuscular stroma and fat. Immunohistochemistry showed PSA expression but

absent staining for CK7, CK 20, CEA and hMSH. The regional lymph nodes were

negatve and clinical investgaton showed no evidence of metastasis. The patent

received no further therapy and during the follow up period of 4 years, he stll

alive, with no evidence of metastasis. Because of the history of mucinous colonic

adenocarcinomas, the diferental diagnosis included primary and secondary

tumors. The former included prostatc adenocarcinoma arising from prostate and

mucin producing urothelial carcinoma arising from the prostatc urethera. The

colon presents one of the most frequent primaries of prostatc metastasis. The

clinical fndings are crucial to rule out metastasis, partcularly endoscopic work up.

Despite the absence of adjacent conventonal of prostatc adenocarcinoma, the

presence of mucinous PIN and the prominent macronucleoli and immunoprofle

were features afrming the diagnosis of primary mucinous prostatc

adenocarcinoma.

P745WHAT ARE THE PREDICTORS OF CANCER PROGRESSION IN PAPILLARY RENAL

CELL CARCINOMA? A CLINICO PATHOLOGIC STUDY OF 86 PATIENTS.

A.R. Husain 1 , A. Yilmaz1, T. Bismar1, J. Zhang, D. Heng2, K. Trpkov1. Department of 1Pathology and Laboratory Medicine, 2Medicine and Oncology, University of

Calgary, Calgary, Alberta.

Background: Papillary renal cell carcinoma (PRCC) is the second most common

Renal Cell Carcinoma (RCC). Because it is uncertain which are the predictors of

PRCC progression and death, we investgated the clinical and pathologic

parameters potentally infuencing the outcome in PRCC. Material and Method:

The study comprised of 86 cases of PRCC, resected from 01/2000 to 07/2007.

Tumor size, nuclear grade, stage and type (I, II or mixed), were evaluated. Time to

cancer progression or cancer death analysis was evaluated by Kaplan-Meier

method and was compared by log-rank test. Results: Patent’s mean age was 60.6

years , male to female rato was 3.1:1 and lef vs right side was 1.1:1. Mean tumor

size was 5.1 cm. Type I was found in 41 patents, type II in 31 and 10 were mixed.

Tumor stage pT1-2 was found in 73 patents and 13 were pT3-4. Nodal metastases

were identfed in only 3 patents. Only 3 patents had disease progression and 2

of them died with metastatc PRCC afer a mean follow-up of 54 months . Only

positve nodes on nephrectomy correlated with cancer progression and/or cancer

death. Conclusions: Patents with PRCC had overall a very good prognosis. Only

nodal status on nephrectomy correlated with cancer progression and/or cancer

death, but limited outcome events precluded more comprehensive survival

analysis.

P747URINARY BLADDER SINUSES – A NOVEL MORPHOLOGICAL LESION WITH

CLINICAL AND PATHOLOGICAL SIGNIFICANCE.

Md. Shahrier Amin, T. Jayasinghe, B.F. Burns, V. da Silva, E.C. Belanger, B.

Djordjevic, B.N. Nguyen, K.T. Mai. Department of Pathology and Laboratory

Medicine, University of Otawa, Otawa, Ontario.

Background: Peculiar changes in the urinary bladder, characterized by segmental

mucosal invaginatons into the submucosa and muscularis propria, were observed

in radical cystectomy specimens. We described and termed these lesions as

urinary bladder sinuses (UBS). The signifcance of these lesions has not been

studied. Methods: 50 consecutve radical cystectomy specimens (49 - carcinoma

with history of BCG / radiaton / chemotherapy, 1 - neurogenic bladder), 20

transurethral resectons of bladder tumor (TURBT) and 20 biopsies were reviewed.

UBS were classifed into superfcial and deep types. Superfcial UBS was defned as

invaginatons of the mucosa (including urothelium, lamina propria and muscularis

mucosa) into the submucosa, while deep UBS was defned as mucosal

invaginatons into the muscularis propria. Superfcial UBS were distnguished from

cystts cystca, and deep UBS difered from intramural ureters by their clef-like

appearance. Results: UBS were ofen associated with cystts cystca and

proliferaton of Von Brunn’s nests. Superfcial UBS were identfed in 13/20 TURBT

specimens. Of the 50 radical cystectomy specimens, superfcial UBS were

identfed in 26 cases, and deep UBS (all with associated superfcial UBS) were

seen in 13 cases. UBS were found to be more located adjacent to scars or invasive

carcinoma than elsewhere in the bladder. Intraepithelial neoplasia involving the

mucosa of UBS was observed in 14 cystectomy specimens. Conclusions: Mucosal

redundancy and hypertrophy of the muscularis propria associated with UBS can

mimic muscle invasive cancer on pelvic examinaton and imaging. They may pose

diagnostc problems with invasive carcinoma. Recogniton of UBS is important,

both pathologically and clinically, in order to avoid over-staging of bladder

malignancies.

P748A MESOTHELIAL CYST IN AN ADRENAL GLAND THAT IS FUSED WITH THE

IPSILATERAL KIDNEY IN A 50-YEAR-OLD WOMAN, AN UNUSUAL CASE.

R.J. Guo MD, PhD, L. Balos, MD, F. Chen, MD, PhD, J. Sun, MD, PhD. Department

of Pathology, State University of New York at Bufalo, Bufalo, New York, USA.

Adrenal cysts are distnctly uncommon and most are endothelial cysts or

pseudocysts. Very few true epithelial or mesothelial cysts have been reported.

Renal-adrenal fusion is a rare anomaly that involves the upper pole of kidney and

is usually identfed as an incidental fnding in nephrectomy specimens or at

autopsy. Here we report an unusual case of a true mesothelial cyst in an adrenal

gland that is fused with the ipsilateral kidney. The patent was a 50-year-old

woman who presented with right fank and back pain. A CT scan showed a large

right adrenal hypodense mass. The resecton specimen shows a 6 cm adrenal cyst

lined with cuboidal to fatened cells without atypia. The lining cells are positve

for pancytokeratn, calretnin and HBME-1, consistent with a mesothelial cyst. Of

interest, the adrenal gland is directly adherent to the kidney, with no intervening

fbrous capsule or other connectve tssue. The adrenal cortex that appears as

clusters of clear cells in the kidney parenchyma raises a diferental diagnosis of

renal clear cell carcinoma. This is excluded by negatve CD10 and EMA stains. The

adrenal cortcal origin is confrmed by positve inhibin stain.

12

P749PRIMARY RENAL CARCINOID TUMOR: RARE CASE REPORT.

B. Fahmy1, S. Tauqir2, S. Alowami2, D. El Demellawy3,4. Pathology Departments: 1Chatham-Kent Health Alliance, Chatham, Ontario; 2McMaster University,

Hamilton, Ontario; 3Northern Ontario School of Medicine, Sudbury, Ontario; 4William Osler Health Center, Brampton, Ontario.

Primary renal carcinoid (rc) is an extremely uncommon tumor and litle is known

about its clinicopathologic features and prognosis. We describe a case of rc in a

57-year-old man presents with loin pain. CT shows a right kidney enhancing 3 cm

mass. On resecton, a tan tumour displaying microscopic trabecular architecture

populated with monotonous cells is noted. Immunohistochemistry shows tumor

expression of chromogranin, CD56 and synaptophysin. We report a rare case of

rc. Because neuroendocrine cells are not present in normal kidneys, when rc is

encountered, it is important to rule out metastatc disease. A primary rc is

speculated to arise as a derivaton from misplaced neural crest during em-

bryogenesis.

P750MALIGNANCIES IN THE RENAL TRANSPLANT POPULATION: THE ST. MICHAEL’S

HOSPITAL EXPERIENCE.

R. Saleeb1, H. Faragalla1, G.M. Yousef1,2, R. Stewart3, C.J. Streutker 1,2 . 1Department

of Laboratory Medicine, University of Toronto, Toronto, Ontario; Departments of 2Laboratory Medicine and 3Urology and the Li Ka Shing Knowledge Insttute, St.

Michael’s Hospital and the University of Toronto, Toronto, Ontario.

Introducton: Previous publicatons have shown increased incidence of various

malignancies amongst the renal transplant populaton. The objectve of this study

was to analyze the rate and types of malignancies occurring in St. Michael’s

Hospital renal transplant populaton, and to determine whether the rate, types

and outcomes of these malignancies were comparable to those previously

published. Methods: The study was approved by the SMH Research Ethics Board.

The clinical and pathologic history of all of the patents in the St. Michael’s

Hospital Renal Transplant Clinic database was retrospectvely reviewed from

approximately 1970 to the present. Review of the records and pathology of these

1584 patents was performed using the hospital’s digitalised clinical and pathology

data bases. Results: Amongst the 1584 patents with renal transplants, 99

patents with post-transplant malignancies were identfed. The highest incidence

amid the malignancies were non-melanoma skin malignancies, (SCC, BCC and

Kaposi Sarcomas) amountng to a total of 37 patents having 69 separate tumors

(2.3% of all the transplant patents, 37% of transplant patents with tumours).

Following skin tumours in incidence were gastrointestnal tract (GIT) malignancies

(24 patents, 1.5% of patents, 24% of patents with tumors), then urological

tumours (kidney and bladder) (13 patents, 0.8% of patents, 13% of patents with

tumors), then post-transplant lymphoproliferatve disorders (PTLD) (8 patents,

0.5% of patents, 8% of patents with tumors) , prostate (7 patents, 0.4% of

patents, 7% of patents with tumors), endometrium (6 patents, 0.3% of patents,

6% of patents with tumors), thyroid (2 patents, 0.1% of patents, 2% of patents

with tumors), ovary (1 patent, 0.06% of patents, 1% of patents with tumors) and

lung carcinomas (1 patent, 0.06% of patents, 1% of patents with tumors). The

average patent age when malignancies were discovered was 56. Of the 99

patents, 14 died of malignancy, with the highest mortality being in the GIT

malignancies (6 out of the 14 cases). Second in mortality were the PTLD and skin

tumour groups, with 3 patents in each dying secondary to the malignancy.

Discussion: Informaton on the incidence and outcome of various malignancies in

renal transplant patents is important in designing guidelines for the follow up of

these patents regarding tumor screening and preventon of malignancies. The

rate of malignancies in our renal transplant group is comparable to that reported

at other centres.

P751METASTATIC ADENOID CYSTIC CARCINOMA MASQUERADING AS RENAL CELL

CARCINOMA IN A PATIENT 10 YEARS AFTER EXTIRPATION OF TRACHEAL

ADENOID CYSTIC CARCINOMA.

N. Aldaoud1, J. Sweet1, N. Fleshner2. 1Department of Pathology and Laboratory

Medicine, 2Department of Urology, Toronto General Hospital, Toronto, Ontario.

Adenoid cystc carcinoma is an aggressive, ofen indolent tumor, with high

incidence of distant delayed metastasis. We describe a case of 40 year- old woman

who underwent partal nephrectomy for an incidental solitary lef solid renal mass

during her follow up for a tracheal adenoid cystc carcinoma resected in 2001. The

patent received radiotherapy to her neck in 2001 but in 2003 she had lung

metastasis which was excised. In 2011, abdominal CT scan found a renal mass

which was suspicious for a renal cell carcinoma. The partal nephrectomy

specimen showed a well circumscribed white, tan solid mass measuring 2.6 x 2.1 x

1.3 cm. On microscopic examinaton, the mass had the characteristc cribriform

patern of adenoid cystc carcinoma, with dark compact angular nuclei

surrounding pseudoglandular spaces with basement membrane-like material,

together with small true glandular lumen. To our knowledge, only 10 cases of

adenoid cystc carcinoma metastatc to the kidney have been reported. This case

emphasizes the unique slow-growing nature of this tumor and the importance of

long follow-up afer surgery.

P752MALIGNANCIES ARISING IN ALLOGRAFT KIDNEYS: A CASE SERIES.

R. Saleeb1, H. Faragalla1, G.M. Yousef1,2, R. Stewart3, C.J. Streutker1,2. 1Department

of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario; 2Department of Laboratory Medicine, Li Ka Shing Knowledge Insttute, St.

Michael’s Hospital, Toronto, Ontario; 3 Department of Urology, Li Ka Shing

Knowledge Insttute, St. Michael’s Hospital, Toronto, Ontario.

Introducton: Cancer in the post kidney transplant populaton has been a rising

concern in many publicatons causing a debate regarding the need for increased

post transplant surveillance for certain types of cancer. Renal carcinoma is one of

the most common cancers to occur in the transplant populaton, almost always

arising in diseased natve kidneys. Rarely, tumors arise in the transplanted kidney.

Our case series reports three cases of malignancy in these allograf kidneys.

Methods: The renal transplantaton data base at St. Michael’s hospital, which

consttuted 1584 patents, was reviewed for diagnoses of malignancies arising in

the post transplant period. Cases of tumours arising in the allograf were

identfed, and the reports and pathology slides were reviewed. Results: Four

cases of malignancies arising in the allograf kidney were identfed among our

kidney transplant populaton; this is a signifcant proporton (3.9%) of the post-

transplant malignancies as a total of 101 malignancies were identfed in the 1584

patents. One patent developed a high grade urothelial carcinoma in the pelvis of

the donor kidney 9 years post transplant and 6 years post BK virus infecton. The

other 3 cases were renal cell carcinomas, developing 1 year, 9 years, and 16 years

post transplant. One case was clear cell carcinoma, Fuhrman Grade 3, pT1a. One

case showed renal cell carcinoma with areas of both clear cell and papillary

architecture, Fuhrman Grade 3, pT1b. The third case was pure papillary renal cell

carcinoma, Fuhrman Grade 1, pT1a. Both of the tumours with papillary

diferentaton showed cytokeratn 7 and racemase staining. Discussion: Previous

reports suggest that malignancies in allograf kidneys (other than post transplant

lymphoproliferatve disorders) were rare. We identfed 4 tumours, three renal cell

carcinomas and one urothelial carcinoma, in 1584 transplant patents. Tumors

developed 1-16 years afer transplantaton. One patent had prior BK virus

infecton: there is a correlaton in previous literature between BK virus infecton

and urothelial carcinoma. While the rate of malignancy in allograf kidneys is

small, screening of the donor kidneys by ultrasound and/or urine cytology may be

of use in detectng these lesions

13

P753DETECTION OF SERINE-105 PHOSPHORYLATION ON ER β AND ITS CORRELATION

WITH THE CLINICAL AND PATHOLOGIC STATUS OF THE PROSTATE CANCER.

I. Siddiqui MD1, Y. Liang MD1, H.-M. Lam PhD2, J. Wang, MD2. 1Department of

Pathology and Lab Medicine, University of Cincinnat, College of Medicine; 2Department of Environmental Health, University of Cincinnat, College of

Medicine.

Estrogen receptor-beta (ERβ) plays a crucial role in the development of cancers.

Phosphorylaton of ERβ evoked by ligands and growth factor mediated rapid

pathways has been implicated in stmulaton of receptor actvaton. A novel

serine-105 (S105) phosphorylaton site was identfed in vitro kinase assays using

extra cellular signal regulated kinases 1and 2 (ERK1/2) and p38.The purpose of this

study was to investgate the expression of ERβ and S105 in normal and cancer

cells of prostate and correlatng the expression with the stage as well as grade of

the tumor. We analyzed immnunohistochemistry results from 50 cases of prostate

cancer archival specimens. pS105 was detected in both the nucleus and cytoplasm

of prostate cancer cells and their adjacent benign basal and luminal epithelial

cells. In general nuclear staining was higher as compared to cytoplasmic staining

(p<0.05). Prostate cancer acini displayed higher nuclear and cytoplasmic staining

based on Allred score when compared to adjacent benign acini. In order to

understand the role of pS105 on ERβ1 we immunostained each case with an ERβ1

specifc antbody and we found that nuclear ERβ1 staining decreased although not

statstcally signifcant (p>0.05) in higher grade cancers as compared to benign

epithelium. This is in contrast to the results of S105 staining in higher grade

cancers. In conclusion, generally a stronger nuclear staining as compared to

cytoplasmic staining was found but no correlaton was found between ERβ

positvity, TNM staging and PS105 staining intensity.

Benign Cancer

Nucleus 6.8+/- 0.1 7.4+/- 0.1

Cytoplasm 4.6+/- 0.3 5.9+/- 0.2

A. p<0.01 compared to cytoplasmic staining

B. p<0.01 compared to normal tssue.

Quantfcaton of p105-ERβ immunohistochemical staining in prostate

sprecimens.Allred score (0-8) represents the sum of the staining intensity (0-3)

and coverage of positve stain (0-5)

P754MALT LYMPHOMA OF THE PROSTATE – A CASE REPORT.

M. Toal, S.L. Ofman, S.K. Murray. Department of Pathology, Dalhousie University,

Halifax, Nova Scota.

Primary MALT lymphoma of the prostate is rare. Clinicopathologic features are not

yet well clarifed and more cases are needed to address this defcit. Herein, we

report the tenth case of MALT lymphoma of the prostate. Our patent is an elderly,

75 year old male who presented with gross haematuria and an elevated PSA . He

underwent TURP for symptoms atributed to a clinical diagnosis of benign

prostatc hyperplasia. Pathological examinaton showed substantal, nodular

collectons of small, uniform lymphocytes with perinuclear clearing. The

lymphocytes were positve for CD20 and BCL2, equivocal for CD5 (focal and weak)

and negatve for CD10, CD23 and cyclin D1. Molecular analysis showed clonal

proliferaton of B lymphocytes. The fndings were consistent with a diagnosis of

MALT lymphoma The patent later had a contrast enhanced CT of the chest,

abdomen and pelvis that showed a mildly enlarged paratrachael lymph node and

notable lymph nodes in the periaortc region and in the cardiophrenic fat pad.

Currently, the patent is being investgated and managed by a haem-oncologist.

The few previously reported cases suggest that MALT lymphomas arising in this

locaton will have an indolent course with a positve response to chemotherapy.

P755PLASMACYTOID VARIANT OF UROTHELIAL CARCINOMA: RARE CASE REPORT.

D. El Demellawy1,2, B. Bishwajit1,3, S. Tauqir5, S. Alowami5, M. Bonin1, 4. 1Northern

Ontario School of Medicine, Sudbury, Ontario; 2Departments of Pathology, William

Osler Health Centre, Brampton, Ontario; 3Service of Urology, Sudbury Regional

Hospital, Sudbury, Ontario; 4Departments of Pathology, Sudbury Regional

Hospital, Sudbury, Ontario; 5McMaster University, Hamilton, Ontario.

Plasmacytoid variant of urothelial bladder carcinoma is rare. A 50-year-old man

presented with hematuria, 3 years ago. CT scan revealed a large urinary bladder

solid mass with bilateral hydronephrosis. Metastatc workup was negatve. A

biopsy revealed non invasive papillary urothelial carcinoma. The patent was

followed by yearly cystoscopy and cytology. The later showed atypical urothelial

cells. This year the patent had a transurethral resecton of the urinary bladder

tumor which revealed a non invasive high grade urothelial carcinoma. The patent

subsequently had a radical cystoprostatectomy. Final pathology revealed

plasmacytoid variant of urothelial carcinoma with extensive vascular invasion and

extension to the perivesical adipose tssue. We present a rare variant of urothelial

carcinoma with detailed discussion of the morphological and immunophenotypic

clues that characterises this variant.

P801EFFICACY OF TBL IN PBL CURRICULUM.

K. Anwar, A.A.Sheikh, N.R. Dash. Clinical Science Department, College of

Medicine, University of Sharjah, Sharjah, United Arab Emirates.

College of Medicine in University of Sharjah, United Arab has envisioned student

centered community oriented problem base curriculum. We introduced two

variants of TBL in pathology courses to seek their efcacy in our present problem

based learning (PBL) curriculum. In resource session TBL (RS-TBL) the students

were assessed individually for individual-readiness assurance test (IRAT) and in

group for group readiness assurance test (GRAT) for their preparedness of the

topic content and objectves provided them earlier. In review session TBL (RVS-

TBL) the same strategy was adopted for individual signifcant learning assurance

test (ISLAT) and group signifcant learning assurance test (GSLAT) respectvely for

the entre week learning actvites related to that week problem. The study

involved 106 second year students during their Cardiovascular/ Respiratory (8

weeks) and Hematology units (3 weeks).The frst 8 weeks of the course were

assessed as RS-TBL and the last 3 weeks as RVS-TBL.The attudinal survey was

devised specifcally for comparing PBL resource sessions with TBL session and RS-

TBL with RVS-TBL. In RS-TBL and RVS-TBL performance for individual was 36.25%

and 40% (p<0.0001) respectvely. Same trend was observed for the group

performance 70.00% vs. 83.30% (p<0.0001). Comparing between the RS-TBL and

RVS-TBL, we found that individual student and group performance was beter in

the later (p<0.0001). The result of the student attudinal survey indicated an 88%

agreement that TBL enhanced their understanding of Pathology concepts and

critcal analysis. Most of the partcipants (85%) found RVS-TBL to be more useful.

Keeping in view relatvely beter and statstcally signifcant performance in RVS-

TBL compared to RS-TBL, and the students' preference in their attudinal survey,

we recommend that RVS-TBL should be adopted to enhance the philosophy of

small group teaching in the perspectve of PBL curriculum.

14

P804PRECURSOR LESIONS AND PROGNOSTIC FACTORS IN PRIMARY PERITONEAL

SEROUS CARCINOMA.

S. Lee 1 , G. Nelson2, A. Kilmowicz1, E.Kornaga3, S. Petrillo3, A. Magliocco3, M.

Duggan1. 1Anatomic Pathology, Foothills Medical Center, Calgary, Alberta; 2Gynecologic Oncology, Foothills Medical Center, Calgary, Alberta; 3Molecular

Pathology, Foothills Medical Center, Calgary, Alberta.

Objectives: Recent investgatons suggest that ovarian serous carcinomas may

evolve from p53 signatures, a group of 12 consecutve tubal epithelial cells with

nuclear p53 accumulaton (Am J Surg Path 2007;31:161-169). The objectve of this

study is to investgate the relatonship between p53 signatures, tubal

intraepithelial carcinoma (TIC) and primary peritoneal serous carcinoma (PPSC).

Design: 22 cases of PPSC processed between 2000 - 2008 were reviewed to

identfy areas of atypia, TIC, and carcinoma. Sectons of omentum, fallopian tubes

(FT), and ovaries were stained with p53 to identfy p53 signatures. p53 intensity (0

= negatve, 1 = weak, 2 = intermediate, 3 = strong) and proporton (0 = none, 1 =

1%, 2 = 10%, 3 = 33%, 4 = 67%, 5 = 100%) were recorded. The highest

measurements were added to form a p53 score. Ovarian surface epithelium (OSE)

and cortcal inclusion cysts (CIC) were scored separately. Results: 4 cases were low

grade and 18 were high grade. All cases were stage 3 and 4. Precursor lesions

(atypia, p53 sigs, TIC) were present in 45%, located at the fmbriated end of the FT.

p53 signatures were identfed in 29%. p53 scores for PPSC and FT were similar

(average 5.1 and 4.2) and signifcantly higher than p53 scores for OSE and CIC

(average 0.7 and 1.5). Conclusion: p53 scores are signifcantly higher in PPSC and

FT epithelium than OSE and CIC. These preliminary results suggest that recently

described precursors in the FT may have a role in the carcinogenesis of PPSC.

P806ENDOCERVICOSIS OF THE UTERINE CERVIX: A CASE REPORT OF A RARE ENTITY

AND COMPARISON TO ITS NEOPLASTIC MIMICS.

L. Hamilton, M. Khalil. Dept of Pathology and Laboratory Medicine, University of

Calgary, Calgary, Alberta.

Objectve: Endocervicosis, the presence of benign endocervical-type glands in

ectopic sites, is unusual and described most frequently in the bladder.

Involvement of the outer wall of the uterine cervix is very rare and represents a

diagnostc pitall, as it may resemble some malignant and borderline lesions.

Methods: This case study describes the incidental fnding of endocervicosis in the

outer uterine cervix of a hysterectomy specimen for menorrhagia/ leiomyomata.

Histologic comparison is made between endocervicosis and its mimics: minimal

deviaton adenocarcinoma (MAC), and non-invasive uterine implants from a

seromucinous borderline ovarian tumor (BOT). Results: All three cases shared an

architectural patern of haphazardly arranged dilated glands within the wall of the

uterine cervix; the glands were lined by mucinous columnar/cuboidal cells with

mildly atypical nuclei. In contrast to endocervicosis, MAC and the implants had

scatered mitoses and focal nuclear stratfcaton. The glands of endocervicosis

and the implants were confned to the outer wall, whereas the deeper glands in

MAC were contnuous with a glandular proliferaton in the endocervical mucosa,

which focally had a component of poorly diferentated carcinoma. In the case of

the seromucinous BOT, the mucinous glandular uterine implants resembled the

mucinous component of the ovarian tumor; no serous component was identfed

in the implants. Conclusion: There are striking morphologic similarites between

endocervicosis and its neoplastc mimics. Examining these lesions in isolaton may

pose a challenging diferental diagnosis. Difcultes can be resolved by the

careful assessment of the locaton of the lesion, the overall architecture, and the

surrounding stroma. The importance of the clinical context cannot be

overemphasized.

P807CORRELATION OF CERVICAL SMEARS WITH HISTOLOGY AND FREQUENCY OF HUMAN PAPILLOMA VIRUS (HPV).M.H. Bukhari1, M. Zainan1,2, G. Ahmad1, I. Qaderi1,2, I.M. Bakhsi1,2. 1Department of

Pathology King Edward Medical University, Lahore, Pakistan; 2Natonal University

of Science and Technology, Islamabad, Pakistan.

Background: The frequency of HPV in cervical carcinoma is rising in our country

and conventonal cervical smears by Papanicolaou method (Pap smears) are the

popular tests for its early detecton in Pakistan. The study was conducted to

detect the HPV from premalignant and malignant cervical neoplasms by PCR.

Materials and Methods: 102 already diagnosed Pap smears for premalignant and

malignant cervical neoplasm were compared for histology and PCR for detecton

of HPV and its subtype. Results: The 46/102 (45%) cases were low grade

squamous cell intraepithelial lesions (L-SILs), twenty two (21.5%) cases were high

grade squamous cell intraepithelial lesions (H-SILs), 14 cases (13.7%) were

squamous cell carcinomas(SCC), 6 (5.8%) cases showed features of

adenocarcinoma, ten (9.8%) cases showed cytology of atypical squamous cells of

undetermined signifcance (ASCUS) and 4 (3.9%) cases were of atypical glandular

cells of undetermined signifcance(AGUS).Out of 79 malignant cases 67/79 (85%)

were positve for HPV and among them 59/67(89%) cases were of HPV-16 and

7/67(11%) cases of HPV-18. Out of 12 cases of adenocarcinoma 5 (41%) showed

positvity for HPV-16. Conclusion: Premalignant and Malignant cervical lesions are

not common in our patents and Pap test is an efectve diagnostc modality. HPV

is a risk factor for inducton of this carcinoma and may be prevented by preventve

vaccinaton. Genotype HPV-18 is more frequent than others.

P808CLINICO-PATHOLOGICAL DETERMINANTS OF PREMALIGNANT AND MALIGNANT

POLYPS OF THE LOWER FEMALE GENITAL TRACT.

C. Fauth 1 , A. Franko2, Q. Duan3, S. Wood4, M.A. Duggan2,4. 1Department of

Pathology, Britsh Columbia’s Children’s Hospital, Vancouver, Britsh Columbia;

Departments of 2Pathology and Laboratory Medicine, and 4Obstetrics and

Gynecology, University of Calgary, and 3Clinical Trials Unit, Tom Baker Cancer

Centre, Calgary, Alberta.

Objectve: To identfy clinical and pathological determinants of premalignant and

malignant polyps of the lower female genital tract. Methods: Using a case

control design, clinical and pathological variables of all premalignant and

malignant vaginal polyps examined over 6 years at a single insttuton were

compared to a control group of benign cervical and vaginal polyps. Variables were

abstracted from patent chart and pathology glass slide reviews and diferences

were tested for signifcance using univariate analysis. Signifcance was set at

p<0.05. Data and results: Following the pathology review, there were 11 CIN, 2

endometrial hyperplasias and 8 invasive carcinomas. The 21 polyps were

randomly matched to 42 benign polyps. The distributon of variables by

premalignant-malignant and benign diagnoses fuctuated and statstcally

signifcant diferences between them was only seen in age at surgery. The

frequency of premalignant-malignant polyps in women 40 years and younger was

double the frequency of benign polyps (p=0.04). In a separate analysis, polypoid

invasive carcinoma was six tmes more frequent amongst those older than 60

years and this diference approached statstcal signifcance (p=0.09).

Conclusions: Age at presentaton is a signifcant determinant of premalignant and

malignant polyps of the lower female genital tract. Premalignant polyps are more

frequent in younger and malignant polyps are more frequent in older women.

15

P809MORPHOLOGICAL EFFECTS OF CHEMOTHERAPY ON OVARIAN SEROUS

ADENOCARCINOMA.

I. Siddiqui, M.M. Weir. Dept. of Pathology, London Health Sciences Center &

University of Western Ontario, London, Ontario.

Background: Ovarian carcinomas are treated either with debulking surgery and

post-operatve chemotherapy, or neo-adjuvant chemotherapy followed by interval

debulking surgery. Chemotherapy efects on ovarian carcinomas have not been

well studied. We sought to 1) assess chemotherapy changes in only ovarian serous

adenocarcinomas by comparing pre- and post-chemotherapy samples; and 2)

examine grading post-chemotherapy. Materials and methods: Archival cases of

serous adenocarcinomas were reviewed: one group included pre-treatment

biopsies (n=7) with comparison to subsequent post-chemotherapy resectons;

other group included resectons prior to chemotherapy (n=14). Cases evaluated

for treatment efects (necrosis, bizarre nuclei, epithelial-stromal rato, old

hemorrhage, giant cell reacton, fat necrosis, foamy changes, ballooning and

cholesterol clefs); treatment response (none, minimal or marked) and grading

(Silverberg). Results: The epithelial to stromal rato was increased in all treated

cases and correlated with the degree of treatment response. Four cases showed

lobular carcinoma-like features. Bizarre nuclei, cholesterol clefs, giant cell

reacton, foamy macrophages and intratumoural lymphocytes were nearly

exclusively seen in treated cases. Post- compared to pre-chemotherapy grade

remained the same or increased in 6/7 cases. Bizarre nuclei were a pitall for

nuclear atypia post-treatment. Conclusion: Our study highlights specifc

morphological changes in serous adenocarcinomas treated with chemotherapy,

which may be linked to treatment response. Grading post-treatment was similar

to pre-treatment (remains high grade 2 or 3).

P811CLASSIFICATION OF 4, 402 POLYPS OF THE LOWER FEMALE GENITAL TRACT.

C. Fauth 1 , A. Franko2, Q. Duan3, S. Wood4, M.A. Duggan2,4. 1Department of

Pathology, Britsh Columbia’s Children’s Hospital, Vancouver, Britsh Columbia;

Departments of 2Pathology and Laboratory Medicine, and 4Obstetrics and

Gynecology, University of Calgary, and 3Clinical Trials Unit, Tom Baker Cancer

Centre, Calgary, Alberta.

Objectve: To establish a pathological classifcaton and calculate the frequencies

of polyps arising in the vagina and cervix. Methods: The pathology diagnoses of

all cervico-vaginal polyps examined over 6 years at a single insttuton were

classifed using standard pathological principles and frequencies calculated. The

glass slides of all vaginal and premalignant-malignant polyps were reviewed

together by a 3 person panel. Data and Results: Out of 4,402 polyps, 4,340

(98.6%) were cervical and 62 (1.4%) vaginal. There were 4,281 (97.3%) epithelial,

32 (0.7%) mixed epithelia and mesenchymal, 17 (0.4%) mesenchymal and 72

(1.6%) unsatsfactory polyps. Benign epithelial polyp (4,281, 97.3%) was the most

frequent category and benign endocervical polyp consttuted the most (n=4,137,

94.0%) frequent subcategory. All 62 (1.4%) premalignant-malignant polyps were

epithelial and CIN 1 formed the majority. The mixed polyps were all fbroepithelial

polyps and the mesenchymal polyps mostly consisted of leiomyomata. The review

of the vaginal polyps as benign (n=61) and premalignant (n=1) agreed with the

original. Since there was agreement for only 21 (33.9%) of the 62 premalignant-

malignant polyps, the overall premalignant-malignant polyp frequency is closer to

0.5%. Most of the disagreement was due to a downgrading of CIN I to benign.

Conclusions: The majority of polyps in the lower female genital tract are cervical

and benign endocervical polyps. Vaginal polyps are uncommon and rarely

malignant. Premalignant -malignant polyps are uncommon.

P813CLINICO-PATHOLOGICAL DETERMINANTS OF VAGINAL POLYPS OF THE LOWER

FEMALE GENITAL TRACT.

C. Fauth 1 , A. Franko2, Q. Duan3, S. Wood4, M.A. Duggan2,4. 1Department of

Pathology, Britsh Columbia’s Children’s Hospital, Vancouver, Britsh Columbia;

Departments of 2Pathology and Laboratory Medicine, and 4Obstetrics and

Gynecology, University of Calgary, and 3Clinical Trials Unit, Tom Baker Cancer

Centre, Calgary, Alberta.

Objectve: To identfy clinical and pathological determinants of vaginal polyps.

Methods: Using a case control design, clinical and pathological variables of all

vaginal polyps examined over 6 years at a single insttuton were compared to a

control group of cervical polyps. Variables were abstracted from patent chart and

pathology glass slide reviews and diferences were tested for signifcance using

univariate analysis. Signifcance was set at p<0.05. Data and Results: The 62

vaginal polyps were randomly matched to 126 cervical polyps. Following the

pathology review, 61 (98.4%) vaginal polyps were benign and fbroepithelial polyp

(n=28, 45.2%) was the most frequent type. Although the distributon of variables

by anatomical locaton fuctuated, statstcally signifcant diferences between the

2 locatons did occur. Vaginal polyps were three tmes more frequent amongst

women 40 and younger and twice as frequent amongst those 60 plus (p<0.001).

Additonally, vaginal polyps were larger with a mean size of 1.5 cm compared to

1.1 cm for cervical polyps (p=0.001) and the frequency of multple polyps (>/=2)

was nearly three tmes greater (p=0.04). Conclusions: Age at presentaton, polyp

size and number of polyps are signifcant clinico-pathological determinants of

vaginal polyps. Vaginal polyps occur more frequently in younger and older

women, and are more frequently multple and of larger size.

P814VAGINAL SPINDLE CELL EPITHELIOMA: A CASE REPORT AND REVIEW OF THE

LITERATURE.

E. Mahe BSc, MD 1 , M. Bishara MBBCh, PhD, FRCPC2, D. El Demellawy MBBCh, PhD,

FRCPC3,4, F. DeNardi, MD, FRCPC1, S. Alowami MBBCh, FCAP, FRCPC1. 1Department

of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario; 2Department of General Pathology, Grand River Hospital, Kitchener, Ontario; 3Department of Pathology and Laboratory Medicine, William Osler Health Care,

Ontario; 4Northern Ontario School of Medicine, Brampton, Ontario.

Tumours of the female genital tract may demonstrate a range of histogenic

potental. This histogenic potental is seen in the vaginal spindle cell epithelioma,

an entty previously known as the benign mixed tumour of the vagina. We present

a case of a 52 year old woman who presented to her primary care practtoner

notng a vaginal cyst-like lesion. Primary excision demonstrated a circumscribed

lesion with squamoid cells encased by a bland spindle cell component. Afer an

extensive immunohistochemical work-up was undertaken, a diagnosis of vaginal

spindle cell epithelioma was rendered. The margins of excision were free of

tumour and no subsequent surgical or medical interventon was performed. In

additon to the case report, we also present a detailed review of the literature

focusing on the epidemiology, histologic and immunophenotypic features and

diferental diagnosis of this unique lesion.

P815DOES p53 PREDICT TIME TO FIRST TREATMENT IN MANTLE CELL LYMPHOMA?

S. Nolan 1 , T. Arnason1, A. Robertson2, D. MacDonald2, A. Shawwa1. 1Department of

Pathology, 2Department of Medicine (Hematology), Dalhousie University, Halifax,

Nova Scota.

Background: Currently, treatment strategy for mantle cell lymphoma (MCL) varies

between centers and is debated worldwide. While some advocate for early

aggressive treatment others prefer to “watch and wait” for the development of

signifcant symptoms. A biomarker predictve of early tme to frst treatment

would be useful to make clinical decisions about when to initate treatment.

Immunohistochemical expression of p53 has been shown to be predictve of

overall survival in MCL, but it is unclear if p53 expression is predictve of tme to

frst treatment. Methods: All patents at our insttuton >17 years old diagnosed

with pathologically confrmed MCL from January 1, 1999 to September 28, 2009

were enrolled. Immunohistochemistry for p53 was performed on sectons of

archived, formalin fxed, parafn embedded tssue from the tme of frst diagnosis.

Cases were classifed as immunopositve for p53 when >20% of tumor cells

showed nuclear staining for p53. Time to treatment was determined by chart

review. Results: 35 patents with a confrmed diagnosis of MCL had adequate

archived tssue for analysis and clinical records with long term follow up. The

mean age at diagnosis was 64 years (range 34-88 years). The median tme to

treatment was 56 days in the patents with p53 immunopositve tumors and 33

days in patents with p53 immunonegatve tumors. Kaplan-Meier analysis showed

overlap of the tme to treatment curves for the two groups. The log-rank test

showed no diference in tme to treatment between the two groups (p=0.85).

Discussion: While p53 immunopositvity has been shown to correlate with

decreased overall survival in MCL, it was not predictve of tme to frst treatment

in our cohort of 35 patents. Due to small sample size (although typical of single

centre MCL studies), our study is not powered to defnitvely exclude an

associaton between p53 expression and tme to treatment.

16

P816

SEQUENTIAL BONE MARROW ASPIRATE HEMODILUTION AND CALCULATION OF

RIMG DIFFERENTIAL COUNT CORRECTION FACTOR.

H. Paulin, D. Werner. Department of Pathology and Laboratory Medicine, QEII

Health Sciences Centre and Dalhousie University, Halifax, Nova Scota.

Introducton and Objectves: Sequental bone marrow aspirates required for

diagnosis are presumed to have similar diagnostc characteristcs, but studies

describe that repeated aspirates may become progressively diluted with

peripheral blood. We investgated this phenomenon by analyzing the diference

between frst and second draw diferental cell counts, and devised a correcton

factor to correctly adjust cell counts in the second draw aspirates. Methods: May-

Gruenwald Giemsa stained slides were prepared from frst and second draw

aspirates from seventeen randomly selected patents. Diferental counts were

performed by experienced laboratory technologists and reviewed by a

hematopathologist. Statstcal analysis of the diferental counts included

computng summary statstcs and the Student’s T-test to assess the diferences

between frst and second draw aspirate counts. We then calculated the Rato

between Immature and Mature Granulocytes (RIMG), defned as the sum of

myeloblasts, promyelocytes, myelocytes, metamyelocytes and bands versus

neutrophils. The median RIMG rato between frst and second draw aspirates was

selected as our correcton factor and applied to second draw diferentals to

decrease counts for cells predominantly seen in the peripheral blood

(lymphocytes, monocytes, and neutrophils) and to increase counts for cells

predominantly seen in the marrow (all other cells). Results and Conclusions:

There is a signifcant diference in diferental counts between frst and second

draw aspirates (p<0.05). The median RIMG rato was 1.25 and accurately adjusted

all subpopulatons in the second draw aspirates except for the monocyte count,

which remained signifcantly higher afer RIMG correcton (p<0.05).

P820ADENOSQUAMOUS CARCINOMA OF THE LARYNX.

S. Mokhtari1 D.M.D, S. Sargolzaei1 D.M.D, S. Mokhtari2 D.M.D. 1Department of Oral

and Maxillofacial Pathology, Shahid Behesht University of Medical Sciences,

Tehran, Iran; 2Faculty of Dentstry, Azad University of Medical Sciences, Tehran,

Iran.

Objectve of the Study: Adenosquamous carcinoma (ASC) of the head and neck is

extremely rare in the larynx, with only 34 cases reported in the literature. Here,

we report a case of ASC in the larynx and describe its clinical and histopathological

features with an emphasis on its distnct histology in metastatc lymph node. Data

and Results: A heavy smoker, 52-year-old man with a 1-year history of hoarseness,

presented with a progressive neck mass. Based on the incisional biopsy, diagnosis

of squamous cell carcinoma (SCC) was made. He underwent a total laryngectomy

with bilateral radical neck dissecton. Tissue samples of the tumor showed a

moderately diferentated squamous cell carcinoma. However, lymph node

metastases presented a distnct feature of multple cystc and glandular

structures, lined by columnar mucosal cells. So, further investgatons in primary

tumor sectons were done and glandular features, comingled with squamous

components were found. Therefore, the fnal diagnosis was changed to ASC.

Interestngly the adenoid component and cystc features were dominated in

lymph node metastasis in spite of the fact that the component of squamous

carcinoma consttuted 90% of the primary tumor volume. Five months later, the

recurrence happened; the tumor was resected and the patent was referred for

radiotherapy. He is alive at six month follow up. Conclusion: Adenosquamous

carcinoma is a distnct entty with an aggressive behavior and tendency for early

lymph node metastasis, so it must be distnguished from the most common SCC of

the larynx. Since cystc spaces and mucosal cells are common features of

mucoepidermoid carcinoma (MEC), it was one of the diferental diagnoses of this

case. However, keratn pearl formaton is rarely seen in MECs; also, glandular

structures and epidermoid cells are closely associated with each other in MECs. In

additon, the presence of true glandular features and mucin producton were in

contrast to pseudoglandular spaces and acantholytc epithelial cells in adenoid

squamous carcinoma. In a review of literature we found that supraglotc area is

the most common place for laryngeal ASC. Surgery with neck dissecton is the

treatment of choice.

P821PULMONARY BENIGN METASTASIZING LEIOMYOMA, REPORT OF UNUSUALLY

LONG DELAY IN APPEARANCE, 26 YEARS AFTER RESECTION OF UTERINE

LEIOMYOMA.

H. Huang MD, PhD, L. Balos MD, F. Chen MD, PhD. Department of Pathology, State

University of New York at Bufalo, Bufalo, New York, USA.

Benign metastasizing leiomyoma (BML) is a rare disease which usually presents as

multple pulmonary nodules, several years (average 15 years) afer the resecton

of uterine leiomyoma(s). Only about 100 cases of BML have been reported in

English literature. Here we report an unusual case of BML identfed 26 years afer

resecton of uterine leiomyoma. The patent is a 44-year-old woman who during

workup for a brain lesion that was biopsy-proven astrocytoma, was found to have

an incidental lung nodule in the lef lower lobe of lung. A lung wedge resecton

was performed and a solid, well demarcated, 2.5 x 1.5 x 1.5 cm nodule was

resected. The lesion comprised bland appearing spindle cells without mitotc

actvity that were positve for smooth muscle actn, ER and vimentn. CD117, S100,

Synaptophysin, HMB-45, CD99, calretnin, pancytokeratn and CD10 were

negatve. Ki67 staining showed very low proliferatve index. In conclusion, the

overall morphological and immunohistochemical features, and patent's remote

history of primary uterine leiomyoma supported the diagnosis of pulmonary BML.

P822METASTATIC GIST TO THE SKULL BASE DIAGNOSED 23 YEARS AFTER

PRESENTATION AS A PELVIC SPINDLE CELL TUMOUR.

E. Schollenberg, M.J. Bullock, A.A. Covert. Department of Pathology, Capital

District Health Authority & Dalhousie University, Halifax, Nova Scota.

Background: The defniton of gastrointestnal stromal tumour (GIST) as a distnct

mesenchymal tumour evolved gradually. It was only in 1998, with the discovery

that CD117 (c-kit) is a sensitve marker for GIST, that it became possible to reliably

distnguish it from other enttes commonly considered in the diferental

diagnosis. Case: A 73 year-old woman presented with lef trigeminal neuropathy

and otc efusion. Magnetc resonance imaging demonstrated a 4.7 cm mass

centered in the mastcator space, between the jaw muscles and the skull base.

The patent had a history of a recurrent tumour of the rectovaginal septum, frst

diagnosed in 1987 as a low-grade leiomyosarcoma. Pathology: A diagnostc core

biopsy showed a spindle cell neoplasm with similar morphology to the original

pelvic tumour. The tumour was positve for vimentn, CD34, and c-kit, and was

negatve for S100, actn, and desmin. The archived 1987 material had the same

immunoprofle. The core biopsy was ultmately signed out as metastatc GIST and

it was suggested that the pelvic tumour be reclassifed as GIST in light of the new

immunophenotypic informaton. Discussion: The head and neck area is a very

rare site for metastatc GIST, with only four other reports in the literature.

Presentaton of the primary as a gynecologic tract tumour is also uncommon, but

is a recognized pitall in the diagnosis of extra-gastrointestnal GIST. Most

importantly, however, this case illustrates the importance of considering GIST in

the diferental diagnosis of any persistent, recurrent, or metastatc intra-

abdominal spindle cell tumour originally diagnosed in the era before c-kit. Correct

classifcaton of these lesions allows for the consideraton of tumour-specifc

systemic therapy.

17

P823MUCOEPIDERMOID CARCINOMA OF LARYNX.

S. Mokhtari1 D.M.D, S. Sargolzaei1 D.M.D, S. Mokhtari2 D.M.D. 1Department of Oral

and Maxillofacial Pathology, Shahid Behesht University of Medical Sciences,

Tehran, Iran; 2Faculty of Dentstry, Azad University of Medical Sciences, Tehran,

Iran.

Objectve of the Study: Mucoepidermoid carcinoma (MEC) is the most common

malignant tumor of the salivary glands; however, it is a rare entty in the larynx

and few cases have been reported in the literature. In this paper, a literature

review relatng to laryngeal mucoepidermoid carcinoma has been made and the

tumor behavior according to the grade of diferentaton is discussed. In additon,

diagnostc pitalls and treatment modalites are presented. Methods: In this

paper, a literature review relatng to laryngeal mucoepidermoid carcinoma has

been made to provide deep insights into pathological and clinical features of

laryngeal mucoepidermoid carcinoma; the tumor behavior according to the grade

of diferentaton is discussed. In additon, diagnostc pitalls and treatment

modalites are presented. Results and Conclusion: Mucoepidermoid carcinomas

in the larynx mostly present in the supraglots and patents usually have

progressive hoarseness and dysphagia; however, they ofen spread submucosally

with an intact surface; so primary lesions are not detected by laryngoscopy and

most patents are diagnosed in the advanced stages. High-grade tumors, similar to

MECs in other sites, have few cystc spaces and more solid areas. Therefore, they

are frequently diagnosed as squamous cell carcinoma and as a result laryngeal

mucoepidermoid carcinomas are under-reported. These tumors have a wide

spectrum of clinical behavior from locally invasive to highly malignant. As the main

method for therapy, most agree on wide excision. Since high-grade tumors have

more tendencies for recurrence, combinaton of surgical therapy and radiotherapy

is recommended in these cases.

P824HISTOPATHOLOGICAL EFFECTS OF NEOADJUVANT CHEMO-RADIATION ON

THYMIC NEOPLASMS.

G. Allo, M.S. Tsao, D.M. Hwang. University Health Network, University of Toronto,

Toronto, Ontario.

Background: Locally-advanced thymic neoplasms may be treated with pre-

operatve chemo-radiaton, to potentally improve surgical resectability and

survival. We aim to study the histopathological efects of neoadjuvant chemo-

radiaton (NCR) on thymic tumours. Methods: Retrospectve histopathological

review of post-NCR thymic tumour cases resected at University Health Network

between 2000 and 2010, and comparison with matched thymic tumour cases

treated with primary resecton. Results: Fourteen post-NCR thymic neoplasms

were identfed. Tumours were classifed as thymoma type A (n=1), AB (n=1), B1

(n=3), and B3 (n=3), metaplastc (n=1), indeterminate (n=1), and thymic carcinoma

(n=4). Seven cases showed areas of replacement by proliferaton of bland spindle

cells expressing cytokeratns, in some cases reminiscent of metaplastc thymoma,

comprising up to 70% tumour surface area (Odds Rato OR=6). In two cases, this

resulted in discordant typing between the pre-NCR biopsy and the post-NCR

resecton specimens. Necrosis was present in 6 cases, comprising up to 20%

tumour surface area (OR=2.75). Other features found more commonly in post-

NCR tumours include stromal and peri-tumour hyalinizaton (OR=15), histocytc

infltraton (OR=9.75), myxoid stroma (OR=4.5), cholesterol clefs (OR=3.33),

edema (OR=3.33), multnucleated giant cells (OR=3.33), hemosiderin-laden

histocytes (OR=3.24) and calcifcatons (OR=2.75). Conclusion: Signifcant

histologic changes may be present in thymic neoplasms post-NCR, which in some

cases may interfere with histologic typing in resecton specimens.

P825ISOLATED METASTATIC MUCOEPIDERMOID CARCINOMA (MEC) TO THE BRAIN:

PITFALLS OF CURRENT GRADING SYSTEMS.

D. Ng 1 , R. Seethala2, M. Khalil1, K. Guggisberg1. 1Dept. of Pathology, University of

Calgary, Calgary, Alberta. 2Dept. of Pathology, University of Pitsburgh Medical

Center, Pitsburgh, Pennsylvania, USA.

Background: MEC is the most common primary salivary gland malignancy. Current

grading systems for MEC include the AFIP grading schema and the Brandwein

system. Both systems use features including degree of intracystc component,

mitoses, nuclear atypia, perineural invasion and necrosis to stratfy MEC into low,

intermediate and high grade tumors. However, in additon, the Brandwein system

considers infltratve margins, lymphovascular invasion and bony invasion in their

grading schema. The MECT1-MAML2 gene rearrangement in MEC has recently

emerged as a prognostcator of a less aggressive course and lower mortality risk.

Further, the CDKN2A deleton highlights a subset of MECT1-MAML2-positve MECs

wherein the beneft of translocaton is nullifed with resultant poorer outcomes.

Methods: We describe a case of a 56 y/o female presentng with an isolated right

frontal lobe mass 7 years post-parotdectomy for a primary low-grade MEC (as

graded by AFIP system). Results: The primary lesion had discordant histologic

features with both a prominent cystc component and infltratve borders.

Additonal poor prognostc features were absent. Both the primary MEC and

subsequent brain metastasis were MECT1-MAML2 positve and CDKN2A deleton-

negatve by fuorescent in-situ hybridisaton. Conclusion: To our knowledge, this

case represents the frst and only reported isolated MEC metastasis to the brain.

This case highlights the shortcomings of the current histological grading systems

and tumor genotyping in predictng an aggressive course in an intermediate grade

MEC with presumed favourable features.

P826HIGH FAT DIET RESULTS IN SIGNIFICANT CHANGES IN VISCERAL ADIPOSE TISSUE

IN A RAT MODEL OF DIET INDUCED OBESITY.

L. Narsinghani 1 , A.C. Don-Wauchope1, A.C. Holloway2, H. El-Zimaity3. 1Department

of Pathology and Molecular Medicine and Medicine, 2Dept of Obstetrics and

Gynecology, McMaster University, Hamilton, Ontario; 3Dept of Laboratory

Medicine and Pathobiology, University of Toronto, Toronto, Ontario.

Introducton: Globally obesity has reached epidemic levels. Research evidence

shows that obesity is associated with a state of chronic systemic infammaton

with adipose tssue as the major site of damage. An increase in adipose tssue

macrophages (ATMs) and typical “crowns” of macrophages have been described in

obesity. However, much less is known about the extent and relevance of muscle

tssue macrophages in obesity. Aim: With this project we sought to compare the

macrophage counts in diferent compartments of adipose and muscle tssue in an

animal model of diet induced obesity. We also wanted to study changes in the cell

size of adipocytes in obesity. Methods: Sibling pairs (male and females) from 3

liters were randomized to receive either control or high-fat diet from weaning. At

39 weeks of age, fat (visceral and subcutaneous) and muscle (skeletal and cardiac)

were collected for histological review and assessment of macrophage count using

immunohistochemical stain ED1 (rat homologue of CD68 macrophage marker).

Results: The macrophage count was signifcantly increased in the visceral fat of

animals fed the high fat diet (p value = 0.0043). The macrophage count in

subcutaneous fat, skeletal muscle and cardiac muscle did not show any signifcant

associaton with diet. Adipocyte cell size was signifcantly increased both in the

visceral and subcutaneous fat of animals fed the high fat diet (p = 0.0016 and p =

0.0066 respectvely). There is a correlaton between ATMs and adipocyte size in

visceral fat but not in subcutaneous fat. Conclusion: These fndings support a

hypothesis that visceral adipose tssue infammaton rather than systemic

infammaton is the source of chronic infammaton in obesity.

18

P827INCREASING THROUGHPUT BY MULTIPLEXING DRUGS OF ABUSE ANALYSIS.

A.M. Taylor, M. Yang, D.M. Cox, M. Jarvis. AB SCIEX, Concord, Ontario.

Introducton: Multplexing LC systems, and synchronizing to a single MS,

generates the high throughput needed by modern laboratories that face

increasing sample numbers yet have the expectaton to maintain or improve turn

around tmes. An integrated system has been specifcally designed to synchronize

two LC systems and a mass spectrometer, allowing injectons into two LC streams

in parallel. Methods: Spiked urine calibrators were prepared using Surine

negatve control covering 2 to 20000 ng/mL concentraton ranges for a panel of

drugs of abuse compounds. Sample preparaton included a hydrolysis step and

analyses of the resultng supernatant by LC/MS/MS. The two-stream integrated

multplex LC/MS/MS system consisted of a mass spectrometer, 2 autosamplers, 2

gradient LC pump systems, a shared loading pump, a column oven, and switching

valves for stream selecton; controlled via the mass spectrometer sofware and

device driver. Results: Calibraton curves consistng of nine standard curve

concentratons were constructed for each LC stream, both streams producing

comparable results. Limit of Quantfcaton (LOQ) of 2 ng/mL, for PCP and

methamphetamine, and 20 ng/mL for all the other analytes were obtained. Most

%CVs at the LOQ were below 10%, all within 15%. Accuracy at the LOQ ranged

from 87 to 101%. Conclusions: Using the Multplex LC-MS system in the NIDA-5

analysis, cuts out the tme around the peaks of interest allowing this tme to be

spent performing the injector wash and preloading the next sample. The Multplex

LC-MS system therefore cuts the analysis tme of the singleplex LC/MS/MS

method in half.

P829DEMOGRAPHIC AND HAEMATOLOGICAL FEATURES OF APLASTIC ANEMIA (A

TERTIARY CARE CENTRE EXPERIENCE).

S. Naeem , H. Rafq. King Edward Medical University, Lahore,Pakistan.

Objectve: To complete the data on the demographic and haematological features

of patents diagnosed to have aplastc anemia at a Mayo Hospital over a 5 years

period. Methods: Demographic informaton was collected from patents who

presented with features of aplastc anaemia. Their diagnosis was confrmed by

performing a complete blood count, absolute retculocytes count, bone marrow

aspirate and trephine biopsy. Data and Results: Over the period of fve years i.e

January 2005-December 2010 one hundred and sixteen adult patents were

diagnosed to have aplastc anemia at the Pathology department King Edward

Medical University . Among them 57 were males and 59 females. Their ages

ranged from 15 to 74 years ,with a mean age of 28 years . Out of these 72 (69%)

patents were below the age of 25 years. Fever was the main presentng complain

present in 68 (58.6%) patents. Peripheral counts showed thrombocytopenia to be

present in 100% of cases ,followed by anemia 96%and leucopenia 93% of patents.

Severe aplastc anemia (SAA) was seen in 36%, very severe (VSAA) in 16% and

non-severe aplastc anemia (NSAA) in 48% patents. No obvious cause could be

established for 84% of patents. 18% were found to have either hepatts B virus

markers or antbody to hepatts C at the tme of diagnosis of aplastc anemia.

However it was difcult to establish a cause and efect relatonship with either

drugs or viruses. Conclusion: Aplastc anemia shows equal sex distributon. NSAA

is the most common type of aplastc anemia. Registry for Aplstc Anemia has been

initated.

P830STRIKING MIMICRY OF FOLLICULAR LYMPHOMA BY A CASE OF MANTLE CELL

LYMPHOMA: A POTENTIAL DIAGNOSTIC PITFALL.

S. Varma, D. LeBrun. Department of Pathology and Molecular Medicine, Kingston

General Hospital, Kingston, Ontario.

Mantle cell lymphoma (MCL) is a mature B-cell neoplasm accountng for 5-10% of

non-Hodgkin lymphomas. It is an aggressive lymphoma with a median survival of

three years and currently no defnite treatment optons are available. Although

the pathological diagnosis of MCL is typically straightorward, it can occasionally

mimic other lymphoma types including follicular lymphoma (FL). We describe a

case of MCL diagnosed incidentally in a pericolic lymph node removed during

hemicolectomy for dysplastc polyps. It showed a striking architectural and

cytologic resemblance to grade 1 follicular lymphoma along with abundant

expression of Bcl-2 within the follicle centers. Additonal immunostains revealed

unequivocal expression of CD5 and cyclin D1 characteristc of MCL. This case is

informatve in illustratng the morphological spectrum of MCL. Furthermore, our

fndings support the practce of performing a judiciously designed panel of

immunostains that includes ant-CD5 and ant-cyclin D1 even in cases in which the

morphological fndings appear to justfy an unequivocal diagnosis of FL.

P831SINONASAL SEROMUCINOUS HAMARTOMA WITH FOCAL MYOEPITHELIAL CELLS

AND ASSOCIATED RESPIRATORY EPITHELIAL ADENOMATOID HAMARTOMA.

K.E. Fleming1, B. Perez-Ordonez2, J.G. Nasser1, M.J. Bullock1. 1Departments of

Pathology and Surgery, Queen Elizabeth II Health Sciences Center, Halifax, Nova

Scota; 2Department of Pathology, University Health Network, Toronto, Ontario.

Seromucinous hamartomas are benign lesions of the sinonasal tract. They were

frst described in 1974; since then only a small number of additonal cases have

been reported. They are composed of proliferatons of seromucinous glands and

ducts within a variable fbrous stroma. The serous component typically stains

positvely for S100 (at least focally) and lacks p63 positve abluminal cells. The lack

of myoepithelial/basal cells is an important diagnostc feature of seromucinous

hamartomas; their absence could be a diagnostc pitall leading to an incorrect

diagnosis of low-grade sinonasal adenocarcinoma. We report the case of a

polypoid mass resected from the right posterior nasal cavity and nasopharynx of a

54-year-old woman. The lesion contained a populaton of small and large glands

lined by cuboidal to fatened cells within a hypocellular stroma which varied from

dense and sclerotc to myxoid. In additon to the serous glandular proliferaton,

there was a more superfcial focus of ciliated invaginated surface epithelium and

glands. Throughout the lesion there was no appreciable cytologic atypia, and

there were no morphologic features of malignancy. The histological features were

in keeping with seromucinous hamartoma. Immunohistochemistry showed focal

S100 positvity of the serous glands. However, in contrast to previously reported

cases, both small and large glands focally showed an outer basal layer that was

calponin, p63 and actn positve. Our case demonstrates two important points.

First, seromucinous hamartomas may have focal p63 staining, and complete

absence of p63 should not necessarily be a required feature in the diagnosis.

Second, the ciliated larger glands - in keeping with respiratory epithelial

adenomatoid hamartomas (REAH) - support the suggeston that seromucinous

hamartomas and REAH are a spectrum of lesions, ofen seen together.

19

P833CALRETININ STAINING FACILITATES DIFFERENTIATION OF OLFACTORY

NEUROBLASTOMA FROM OTHER SMALL ROUND BLUE CELL TUMORS IN THE

SINONASAL TRACT.

J.C. Woof1, I. Weinreb2, B.Perez-Ordonez2, M.J.Bullock1. 1Department of

Pathology, Capital District Health Authority and Dalhousie University, Halifax, Nova

Scota; 2Department of Anatomical Pathology, University Health Network (UHN),

Toronto, Ontario.

Objectve: Olfactory neuroblastoma (ONB) has a wide histological diferental

diagnosis that includes other small round blue cell tumors (SRBCT) of the

sinonasal tract. Even with the use of immunohistochemistry (IHC), the correct

diagnosis may be difcult, especially in small biopsies. The purpose of this study is

to determine the usefulness of calretnin and p63, as an aid to distnguish ONB

from other sinonasal SRBCT. Methods: IHC stains for calretnin and p63 were

performed on 21 specimens diagnosed as ONB and 42 other sinonasal SRBCT.

Specimens were retrieved from the fles of the QEII HSC, Halifax and UHN,

Toronto. Results: All but one ONB (20/21) showed calretnin staining, with 15/21

showing >75% of the tumor area staining and 16/21 showing moderate to strong

staining intensity. Only pituitary adenomas (3/3) and a single case of high grade

neuroendocrine carcinoma, NOS (1/2) showed a similar staining patern. None of

the ONBs showed staining for p63. P63 was positve in nasopharyngeal and non-

keratnizing carcinomas, but inconsistently stained sinonasal undiferentated

carcinoma (SNUC) and high grade neuroendocrine carcinomas. Conclusion:

Calretnin appears to be a useful marker to distnguish ONB from other small

round blue cell tumors of the sinonasal tract, partcularly when staining is

moderate/strong and extensive. P63 is consistently negatve in ONB, but its utlity

is limited due to the inconsistent staining of SNUC and neuroendocrine carcinoma,

with which ONB may be confused. The additon of calretnin +/- p63 to an IHC

panel may aid in the distncton of ONB from other sinonasal small round blue cell

tumors that are poorly diferentated, or in small biopsies.

P834AN EFFICIENT APPROACH FOR DIAGNOSIS OF ALPHA-1 ANTITRYPSIN

DEFICIENCY.

P. Tavassoli, G. Ritchie, B. Jung, A. Matman. Department of Pathology and

Laboratory Medicine, St. Paul Hospital, UBC, Vancouver, Britsh Columbia.

Objectve: In most cases (>95%), alpha-1 anttrypsin (A1AT) defciency can be

reliably detected by quanttatve determinaton of A1AT plasma level measured in

concert with isoelectric focusing (IEF). IEF, also referred to as phenotyping is yet

labor intensive test and prone to difcultes in interpretaton. To address these

concerns, molecular diagnostc tests have been developed for the common S and

Z variants. However, they are not widely available in Canada. At St. Paul Hospital,

we have established a cost efectve genotyping method using blood cards (DBS)

to reliably detect common A1AT mutatons. DBS requires no special handling or

storage conditons, is inexpensive to ship and easy to interpret. Methods: Patent

blood samples were collected in EDTA tubes for whole blood DNA extracton using

Roche MagNA DNA isolaton kit. In parallel, samples were collected on DBS and

DNA was extracted using methanol wash followed by distlled water eluton at

95°C. Two pairs of PCR primers that amplify the regions spanning codons 264 and

342 respectvely, and two set of fuorescent probes that detect either Z or S

mutaton were used for PCR amplifcaton before meltng curve analysis using

LightCycler PCR fuorimetric analyzer. Results: 31 patents with low serum level of

A1AT and/or difcult interpretable IEF results were enrolled from Aug 2010- Jan

2011. The quality of extracted DNA from DBS was appropriate and yielded PCR

amplifcaton comparable to those extracted DNA from whole blood. Furthermore,

the genotype results in both methods were 100% consistent. Comparison the IEF

and genotype results showed identcal results aside from a single F allele that was

missed by genotyping. Conclusion and Future Directons: A1AT genotyping from

DNA extracted from DBS appears to be a sensitve, specifc and logistcally simple

alternatve to the IEF method for the inital investgaton of suspected A1AT

defciency. The data set is expanding and full results of the comparison study will

be reported.

P837NON-IMMUNE HYDROPS FETALIS IN VANCOUVER: ARE WE DIFFERENT?

L. Apel-Sarid, C.T. Fauth. Department of Pathology, BC Children’s and Women’s

Health Centre, University of Britsh Columbia, Vancouver, Britsh Columbia.

Objectve: Analyze the causes of non immune hydrops fetalis (NIHF) in fetal

autopsies at the Britsh Colombia Children’s and Women’s Hospital (BCCW) in

Vancouver, Canada. Methods: A retrospectve review of prenatal autopsies

diagnosed with NIHF between 2006-2010 in the department of Pediatric

Pathology at BCCW was done to determine identfable causes for the hydrops.

Results: Among 2018 autopsies conducted in BCCW between 2006-2010 we found

87 cases with NIHF (4.3%).The cause for the NIHF was identfed in 92% of cases,

leaving 7 cases undetermined. The most prevalent cause for the NIHF was fetal

chromosomal abnormalites, identfed in 51cases (58.6%). The most common

chromosomal abnormalites included Monosomy X (n=26), and Trisomy 21 (n=15).

Other chromosomal abnormalites included: 6 cases of Trisomy 18, 3 cases of

Trisomy 13 and a single case of del 5p (cri-du-chat syndrome). Cardiovascular

abnormalites in otherwise normal karyotype fetuses were identfed in 5.7% of

cases (n=5). Parvovirus B19 infecton was confrmed in 3 cases. Other causes

included: Twin-to-twin transfusion syndrome, multple pterygia, adenomatoid

cystc malformaton, diaphragmatc hernia, metastatc congenital neuroblastoma,

fetal gonadoblastoid dysplasia and inferior vena cava thrombus. Conclusion: Only

8% of cases did not have an identfable cause for the hydrops, which is lower than

what has been reported in previous studies. A chromosomal abnormality was

identfed in 58.6% of cases, which is higher than what has been previously

reported. The most common cause of NIHF in this series was fetal chromosomal

abnormalites. The incidence of cardiac malformatons in our series is lower than

previously published, and is likely related to the much higher rate of chromosomal

abnormalites detected.

P838ATYPICAL CARCINOID TUMOR OF LUNG, CLEAR CELL TYPE.

C. Wang, H. Qiu, G. Qing. Department of Pathology, University of Manitoba,

Winnipeg, Manitoba.

Clear cell type of atypical carcinoid tumor is a rare entty that could cause a

diagnostc problem in pathological practce. Here we report a case of atypical

carcinoid tumor, clear cell type. The patent was a 45 year-old women who

presented with a lef upper lobe lung nodule on CT scan. Patent underwent a lef

upper lobe lobectomy. Grossly, the nodule was within the bronchus and was

compressing the adjacent vessels. It was a well-circumscribed tan to yellow-red

variegated tumor measuring 2.4 x 1.8 x 1.6 cm. Histologically, the tumor showed

an organoid arrangement and trabecular patern with mild cytologic atypia. The

majority of the tumor cells show prominent clear cytoplasm. Focal tumor necrosis

was noted. Histochemical stainings for mucin with mucicarmine and PASD were

negatve. By immunohistochemistry, the tumor cells were positve for Pan-CK

(AE1/AE3), CK7, CD56, synaptophysin, chromogranin, and TTF1. They were

negatve for CK20. Ki67 labelling index was about 10-15%. By electronic

microscopy, the tumor cells showed numerous neuroendocrine granules. Based

on the morphologic, immunohistochemical and electron microscopic fndings, we

believe that this is an atypical carcinoid tumor, clear cell type. The diferental

diagnosis for this clear cell tumor should include squamous cell carcinoma or

adenocarcinoma with clear cell features, clear cell tumor of the lung (sugar tumor)

and metastatc carcinoma with clear cell diferentaton (such as renal clear cell

carcinoma and clear cell carcinoma of other organs).

P839DIPNECH, TUMORLETS, AND A TYPICAL CARCINOID: A SPECTRUM OF NEOPLASIA

IN A 48 YEAR OLD FEMALE AND REVIEW OF THE LITERATURE.

A. Stueck MD 1 , Z. Xu MD, FRCPC, FCAP1, G. Buduhan MD, MSc, FRCSC2. 1Department of Pathology, Dalhousie University, Halifax, Nova Scota; 2Department

of Thoracic Surgery, QEII Health Sciences Center, Dalhousie University, Halifax,

Nova Scota.

Difuse idiopathic pulmonary neuroendocrine hyperplasia (DIPNECH) is a rare, pre-

neoplastc entty. We present a 48 year old female with a 15 year history of non-

productve cough , dyspnea, and late onset asthma. Pulmonary functon tests

demonstrated an irreversible, obstructve patern. High-resoluton computed

tomography revealed a difuse, bilateral mosaic patern of air-trapping, with

multple pulmonary nodules. Wedge biopsies of her lungs were completed. The

gross exam of the biopsies revealed a 4.0 x 1.2 x 0.8 cm, yellow-tan, well

circumscribed lesion, and a 0.2 cm grey-white nodule. Histologically, there were

multple lesions identfed. In additon to a typical carcinoid tumor, there were

also proliferatons of neuroendocrine cells confned to the bronchiolar and

bronchial basement membranes, and others extending beyond the basement

membrane, with a maximal dimension of 5 mm. There were minimal mitoses and

no necrosis. These cells stained positve for cytokeratn, chromogranin, and

synaptophysin, and were focally and weakly positve for TTF-1 and Ki67. The

diagnosis is DIPNECH, tumorlets, and a typical carcinoid tumor. We review the

literature available on this spectrum of neoplasia, and discuss the clinical course

and treatment optons.

20

P840ANTERIOR MEDIASTINAL MASS: AN ATYPICAL CLINICAL AND RADIOLOGICAL

PRESENTATION OF A RARE CASE OF ERDHEIM CHESTER DISEASE.

H.S. Sekhon1, R. Padmore1, B. F. Burns1, M. Gomes1, C. Souza2 and S. Sundaresan3. 1Department of Pathology and Laboratory Medicine, 2Department of Radiology, 3Department of Surgery, The Otawa Hospital, University of Otawa, Otawa,

Ontario.

Erdheim-Chester Disease (ECD) is a rare non-familial histocytc disorder of middle

age that mainly involves long bones and commonly presents with bone pain. A 59

year old man presented with an eight months history of dry cough, dyspnoea on

exerton and 30 lbs weight loss. Laboratory workup showed anemia with

abnormal liver functon tests. With a working diagnosis of lymphoma, mult-

detector CT showed anterior mediastnal mass and enlarged retroperitoneal

lymph nodes. US guided biopsies of liver and mesenteric lymph nodes showed no

evidence of lymphoproliferatve disorder which led to mini-thoracotomy to obtain

adequate tssue from mediastnal mass and concurrent wedge biopsies of right

upper and middle lobes. Sectons of anterior mediastnal lesion showed atypical

spindle and typical xanthomatous histocytc proliferaton infltratng into the

mediastnal adipose tssue with scatered Touton-type multnucleated giant cells

and lymphoplasmacytc infltrate. The xanthomatous histocytes stained for

CD68 and Factor XIIIa. Lung sectons revealed difuse subpleural and intralobar

septal thickening with fbrosis and xanthomatous histocytc infltraton similar to

the anterior mediastnal mass and identcal immunoprofle aided to establish a

diagnosis of Erdheim-Chester Disease. Sectons of resected 2nd rib and bone

marrow biopsy also showed xanthogranulomatous infltraton. Post-diagnosis

bone scan demonstrated symmetrical osteosclerotc lesions in long bones. This is

one of the rare ECD cases with atypical clinical and radiological presentaton and

adequate tssue is required to establish specifc diagnosis in such cases.

P841PULMONARY VENO-OCCLUSIVE DISEASE: REPORT OF 3 CASES.

K. Nasim , A.-M. Gillson, D. Lien, B. Chiu. Departments of Lab-Medicine &

Pathology, and Medicine, University of Alberta, Edmonton, Alberta.

Objectve: Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary

hypertension, characterised by progressive pulmonary venous obstructon that

leads to increased pulmonary vascular resistance, right heart failure and

premature death. We report the clinicopathologic data of three cases of this rare

form of pulmonary hypertension. Methods: The clinical and pathologic data of

three cases reported from 2003 to 2010 with pulmonary hypertension due to

veno-occlusive disease from Copath and Netcare were reviewed. Pulmonary

arterial hypertension (PAH) was graded according to Heath-Edwards grading

system. Data: Patents’ ages of 17, 40, and 59 presented with pulmonary

hypertension, and with underlying Noonan syndrome, scleroderma and Hodgkin

lymphoma treated with chemoradiaton and subsequent bone marrow transplant

respectvely. Two of three specimens were bilateral lung explants and one wedge

biopsy. In all cases, the subpleural and interlobular septal veins showed

fbrointmal hyperplasia with eccentric luminal stenosis, segmental arterializaton

and septal thickening. Associated arterial changes were also present,

corresponding to grades II to V. Conclusions: PVOD is a rare disease, but the real

incidence is underestmated due to incorrect diagnosis as idiopathic PAH. PVOD is

associated with a variety of factors, and the correct diagnosis is essental for

referral for lung transplantaton which is the only curatve treatment.

Distnguishing PVOD from idiopathic pulmonary arterial hypertension (PAH) is

ofen difcult but important. Patents with PVOD should be managed only in

centres with extensive experience in PAH due to the risk of pulmonary edema

afer the initaton of PAH-specifc drug therapy.

P842INTRAOPERATIVE FROZEN SECTION CONSULTATION IN THE HAMILTON REGIONAL

LABORATORY MEDICINE PROGRAM (HRLMP): A QUALITY ASSURANCE STUDY.

E. Mahe1, S. Ara1, M. Bishara2, A. Kurian3, S. Tauqir1, N. Ursani4, P. Vasudev1, T.

Aziz1, C. Ross1, A. Lytwyn1. 1Department of Pathology & Molecular Medicine,

McMaster University, Hamilton, Ontario; 2Department of General Pathology,

Grand River Hospital, Kitchener, Ontario; 3Department of Pathology, Bluewater

Health, Sarnia, Ontario; 4Department of Pathology, Oakville Trafalgar Hospital,

Oakville, Ontario.

Correlaton of intraoperatve frozen secton diagnosis with fnal diagnosis can be

an important component of an insttuton’s quality assurance process. A

systematc review of 1207 frozen sectons (from 812 surgical cases) performed in

HRLMP during six months of the 2007 calendar year was performed. The

investgators reviewed the frozen secton and permanent slides from all

potentally discordant cases at a multheaded microscope to arrive at a consensus

pertaining to the type and reason for error, to assess if there had been a potental

adverse impact on immediate clinical management, and to assess whether the

error could been avoided. Frozen sectons were most commonly requested for

head and neck, nervous system and female genital tract specimens. Twenty-eight

frozen sectons (3%) were deferred. Twenty-four discordant diagnoses were

identfed (3% of cases and 2% of specimens). The organ systems showing the

greatest frequency of discordance (relatve to the total number from that system)

were the nervous system, head and neck and lung. Of 25 individual errors

identfed (one case having 2 errors), 17 were due to misinterpretaton, 5 were

related to sampling, 1 was due to technical error and 2 were undeterminable.

There was a potental adverse impact on immediate clinical management in 11

cases, but of these 7 were judged to have been unavoidable. The investgators

concluded that the HRLMP frozen secton-fnal diagnosis discordance rate is

comparable to that in the literature.

P843ON-SITE ADEQUACY ASSESSMENT OF FINE NEEDLE ASPIRATION BIOPSIES.

C.E. Pocrnich, M.M. Weir. Dept of Pathology, London Health Sciences Centre &

University of Western Ontario, London, Ontario.

Background: On-site assessment of fne needle aspiraton biopsies provides

feedback on specimen adequacy and allows for further sampling and ancillary

studies. This study sought to: 1) determine the accuracy of on-site adequacy

assessment (OS) provided by cytotechnologists; and 2) identfy reasons for

diferences between OS and fnal sign-out adequacy assessment (F). Methods: OS

from Oct 09- Dec 10 were compared to F. Re-review of cases with diferences in

OS and F was performed by comparing OS and F slides. Results: Among 797

cases, OS and F comparison yielded 767 (96.2%) concordances and 30 (3.8%)

diferences. Six (0.8%) cases adequate at OS were unsatsfactory at F, and 24 (3%)

cases unsatsfactory at OS were adequate at F. Reasons for diferences in

adequacy included: concentraton of diagnostc material on ThinPrep and/or cell

block (50%); borderline amount of diagnostc material at OS (at “threshold”, 30%);

diagnostc pitalls (10%); and contributory clinical informaton (10%). Conclusions:

Diferences between OS and F occurred in a minority of cases with only rare cases

resultng in an unsatsfactory outcome. An interpretatve issue was identfed in

only a small percentage of cases.

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P844AUTOMATED IMAGE ANALYSIS OF ENDOGLIN AND MICROVASCULAR DENSITY IN

CLEAR CELL RENAL CELL CARCINOMA AND ITS PROGNOSTIC SIGNIFICANCE.

W. Dubinski 1 , M. Gabril2, V. Iakovlev1, Y. Youssef1, K. Kovacs1, S. Metas1, F.

Rotando1, M. Moussa1, C. Streutker1, G. Yousef1. 1Department of Pathology, St.

Michael’s Hospital, University of Toronto, Ontario; 2Department of Pathology,

London Health Sciences Centre, London, Ontario.

Objectves: Endoglin is a novel vascular marker that correlates with prognosis in

numerous tumors. In this study, we provide the frst automated digital assessment

of microvascular density (MVD) in clear cell renal cell carcinoma (ccRCC) using

endoglin and compare our fndings with clinical outcome data. Methods: Fify

cases of ccRCC were immunostained for endoglin and CD31 to highlight tumor

vasculature. Immunostained slides were scanned using an Aperio CS Scanner at

20X magnifcaton, and image analysis was used to count MVD within tumoral and

adjacent normal kidney. Clinicopathologic parameters were collected and

correlated with IMVD. Results: Increased expression of endoglin was associated

with advanced tumor stage (p=0.026). Using a binary cut-of, endoglin-positve

patents had signifcantly lower progression-free survival (p=0.017). When using

endoglin as a contnuous variable, increased expression correlated with reduced

survival (HR:1.87, CI 1.39-2.53, p= <0.001). Conclusion: Automated image analysis

of endoglin expression in ccRCC showed that increased MVD is associated with

higher tumor stage and decreased survival. The advances in digital assessment of

immunohistochemical expression can be helpful in evaluatng and establishing the

clinical signifcance of new prognostc markers for renal cell carcinoma.

P845RENAL AA-AMYLOIDOSIS AND INCIDENTAL RENAL TUMOR.

A. Peyman1, L. Geldenhuys1,2, P. Poyah2. 1Department of Pathology, Dalhousie

University, Halifax, Nova Scota; 2Department of Medicine, Dalhousie University,

Halifax, Nova Scota.

Introducton and Aims: Renal carcinoma may be associated with renal amyloidosis

as a paraneoplastc phenomenon. Methods: We report a case of a 68-year-old

pre-diabetc lady with nephrotc syndrome with 3.5 g/d proteinuria and creatnine

of 233 umol/L. Serology for ant-nuclear antbody and hepatts C virus was

positve, but the remainder of serology was negatve, and there was no

hematuria. Results: Light microscopy showed renal cortex and medulla with a

central focus of tumor with features suggestve of renal carcinoma, expressing

monokeratn, CK7 and CD10, but not vimentn. The adjacent non-neoplastc renal

tssue showed nodular glomerulosclerosis, and intersttal and vascular

eosinophilic material staining positvely for Congo red with apple green

birefringence on polarizaton, consistent with amyloid. There was severe chronic

tubulointersttal change and moderate chronic vascular change.

Immunofuorescence was negatve. Electron microscopy showed randomly

arranged fbrils, 10 nm in diameter, consistent with amyloid. Immunoperoxidase

staining was positve for AA amyloid. Subsequent diagnostc imaging did not

reveal any signifcant renal masses. Conclusions: It is important to be aware that

subclinical renal carcinoma may present with renal amyloidosis as a

paraneoplastc phenomenon, causing signifcant renal disease. Sub-typing of

amyloid may be helpful in suggestng this associated lesion.

P846KIDNEY NERVE SHEATH MYXOMA. A CASE REPORT AND REVIEW OF LITERATURE.

M.M. Mashhour, Sunnybrook Health Sciences Centre, Toronto, Ontario.

Background: Nerve sheath myxomas (NSM) are rare benign cutaneous neoplasms

that may morphologically mimic other myxoid neoplasms of skin and sof tssue.

They are morphologically distnct peripheral nerve sheath tumors with strong

predilecton for the extremites. These tumors have a relatvely high local

recurrence rate when managed by simple local excision. Case: This is a 42 years

old male patent presentng with frank hematuria of three months duraton. CT-

scan was done and a huge solid renal mass was detected. Nephrectomy was done

and grossly: a well circumscribed yellowish mucoid tumor measuring 11.5x10cm.

Microscopically, the lesion was composed of an abundant myxoid matrix, stellate

and spindle-shaped cells arranged in lobules separated by fne fbrous septa with

mild nuclear pleomorphism and scatered mitoses. Immunohistochemically: the

cells were positve for S-100 protein, Vimentn, and focally with GFAP while

negatve for EMA and CD34 which confrm the diagnosis of ( NSM). Discussion: In

1969 Harkin and Reed described an unusual myxoid tumour of probable nerve

sheath tumour and named it myxoma of nerve sheath. Later in 1980, Gallager and

Helwig described similar lesions as Neurothekeoma. Cellular neurothekeoma was

described by Barnhill and Mihm in 1990. Nerve sheath myxoma has also been

referred to as cutaneous lobular neuro-myxoma, perineurial myxoma, and

pacinian neurofbroma Nerve sheath myxoma is a superfcial, multlobulated,

predominantly myxoid, spindle cell neoplasm exhibitng Schwann cell

diferentaton with predilecton for females (2:1), peak incidence in 3rd decade

and more common in trunk and lower extremites. Many pathologists and

dermatologists believe that nerve sheath myxoma is a subtype of neurothekeoma

(so-called myxoid, hypocellular variant of neurothekeoma). The clinical

appearance of nerve sheath myxoma is indistnguishable from that of a

neurothekeoma .Nerve sheath myxoma shows ultrastructural features of Schwann

cell diferentaton. Neurothekeoma exhibits features of fbroblasts (CD34 positve)

or undiferentated stromal cells. It also shows evidence of smooth muscle

diferentaton and negatve staining for S-100 protein. Cases of (NSM) were

reported in Eyelid, oral cavity, paranasal sinuses, Intracranial, spinal, breast and

Subungual regions. Ideally excision needs to be complete with a margin of normal

tssue to reduce the likelihood of recurrence. Diferental diagnosis and a practcal

approach to mimics will be discussed in this paper. Conclusion: To our knowledge,

this is the frst reported case of nerve sheath myxoma afectng the kidney in the

English literature.

P847PARVOVIRUS-ASSOCIATED NEPHRITIS.

A. Peyman1, L. Geldenhuys1,2, P. Poyah2. 1Department of Pathology, Dalhousie

University, Halifax, Nova Scota; 2Department of Medicine, Dalhousie University,

Halifax, Nova Scota.

Introducton and Aims: While parvovirus infecton is usually associated with a

facial rash in children, and less ofen a purpuric rash of the extremites and

arthrits in adults, an aplastc crisis or hydrops foetalis, case reports of renal

involvement do exist. We describe a case of parvovirus infecton associated with

proliferatve glomerulonephrits and acute tubulointersttal nephrits, with the

virus identfed in the renal tssue on polymerase chain reacton. Methods: The

patent was a 63-year-old lady who presented with a three month history of

fatgue, and sudden onset of palpable purpura of the trunk, and upper and lower

extremites, associated with small joint and ankle arthrits, and abdominal pain.

She also had gross hematuria, proteinuria and raised creatnine of 262 umol/L.

Serology screen was negatve, but parvovirus IgM serology was positve. Results:

Light microscopy of a renal biopsy showed mild focal segmental glomerular

proliferaton with no signifcant necrosis. There was moderate tubulointersttal

nephrits with red cells in occasional tubules and focal collectons of eosinophils.

There was also severe chronic vascular change. Immunofuorescence was negatve

and electron microscopy was unremarkable. Polymerase chain reacton for

parvovirus was positve in the renal tssue. Creatnine decreased, and a follow-up

renal biopsy showed only mild tubulointersttal nephrits. Conclusions: It is

important to recognize that parvovirus infecton may be associated with

proliferatve glomerulonephrits and acute tubulointersttal nephrits in adults.

P848TRICHOEPITHELIOMA WITH MONSTER CELLS.

M. Sidiropoulos 1, W. Hanna1,2, D.M.Assaad1,2, and R.Saad1,2. 1Department of

Pathobiology and Laboratory Medicine, University of Toronto, Toronto, Ontario; 2Department of Pathology, Sunnybrook Health Sciences Centre, Toronto, Ontario.

Monster cells imply a strikingly atypical cell with an extremely large and

pleomorphic nucleus. Certain lesions have been known to be ofen associated

with monster cells, including dermatofbroma and basal cell carcinoma.

Trichoepithelioma is a benign adnexal neoplasm with follicular diferentaton.

Numerous diferent forms have been described including solitary, desmoplastc

and multple familial trichoepithelioma. We report a case which had been

misinterpreted as a possible sarcoma, of a 62-year-old woman with a

trichoepithelioma on her medial lef cheek with the unusual histologic feature of

monster cells. Clinically, the lesion presented as a subcutaneous lesion of short

duraton. Histologic examinaton demonstrated characteristc fndings of a

trichoepithelioma and a difuse dermal infltrate of large, atypical epithelioid cells.

Some of these atypical epithelioid cells demonstrated features consistent with

monster cells, including large, bizarre, and pleomorphic nuclei, multple and

prominent nucleoli and abundant cytoplasm. Immunohistochemical staining for

CD68 was positve. Melanocytc and dendritc markers were negatve. A diagnosis

of trichoepithelioma with monster cells was made. To our knowledge, this is the

second reported case.

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P849

GIANT APOCRINE HIDROCYSTOMA: A BREIF RARE REPORT OF UNUSUAL

PRESENTATION.

D. El Demellawy1,2, S. Tauqir 3 , S. Babay3, P. Pastorelo2, S. Elkhawaga1, S. Alowami3.

Pathology Departments: 1Northern Ontario School of Medicine, Sudbury, Ontario; 2William Osler Health Center, Brampton, Ontario; 3McMaster University, Hamilton,

Ontario.

Apocrine hidrocystoma is a benign cystc tumours of the secretory porton of

apocrine sweat glands, frst described by Mehregan (1964). Occurrence in scalp is

rare, with only two cases reported in the English and French literatures. We

report a 60 year old male presented with red brown scalp nodule. The lesion was

mobile and measured 2.8 x 2.0 cm. The lesion was diagnosed clinically as

hematoma and was managed by surgical excision. The excised skin ellipse

contained a cyst surrounded by a 0.1 cm. wall. The cyst contained minimal clear

fuid and its wall was devoid of hemorrhage. Microscopically it showed a

unilocular dermal cystc lesion lined by a double layer of epithelium. The inner

layer contained large columnar cells with eosinophilic cytoplasm which has

luminal decapitaton secreton, denotng apocrine diferentaton. The outer layer

was fat and composed of myoepithelial cells. The lesion was diagnosed as

apocrine hidrocystoma of the scalp. We present an unusual hidrocystoma

presentng as scalp hematoma. Diferental diagnoses considered at the tme

included hemangioma, lipoma, epidermal inclusion cyst, and dermoid cyst.

However the histological fndings are pathognomonic of apocrine hidrocystoma.

Apocrine cystadenoma should be considered in the diferental diagnosis of a large

cystc subcutaneous masses of the scalp.

P850VIRAL-ASSOCIATED TRICHODYSPLASIA SPINULOSA: A RARE CUTANEOUS

COMPLICATION OF IMMUNOSUPPRESSION.

T. Arnason 1 , A. Burns2, S. Murray2, R. Fraser1, N. Walsh1. 1Department of

Pathology, 2Department of Medicine (Dermatology), Dalhousie University, Halifax,

Nova Scota.

A 9 year old girl was seen in dermatology clinic with a mildly pruritc erupton

which developed on completon of a course of chemotherapy (6-mercaptopurine,

methotrexate, vincristne, and dexamethasone) for acute lymphoblastc leukemia.

Her hematological malignancy was in remission and she was systemically well.

Examinaton revealed an erupton of follicular crusted papules with keratotc

spines on the face, including prominent eyebrow involvement. Her shoulders,

arms and legs were also afected. The clinical diferental diagnosis included

keratosis pilaris, generalized molluscum contagiosum, perforatng folliculits, and

atypical infectons. A punch biopsy from the back demonstrated an enlarged hair

follicle. The bulb was abnormal in that it lacked a papilla. Moreover, the matrical

cells were disordered and merged with an expanded inner root sheath with cells

containing large trichohyaline granules. The upper segment of the follicle

including the infundibulum was distended and plugged with keratn. The

histopathological fndings, in the context of the clinical setng led to a diagnosis of

Viral-associated Trichodysplasia Spinulosa (VATS). VATS is a rare virally-induced

follicular erupton (20 reported cases) occurring in immunosuppressed patents

following solid-organ transplantaton or treatment of hematologic malignancies.

The clinical and histopathological characteristcs of this entty are as describe

above and ultrastructural demonstraton of viral partcles in inner root sheath cells

is an adjunct to diagnosis. Treatment with topical antviral agents has yielded

favourable results. Recently, a novel human polyoma virus (TSPyV), closely related

to the Merkel cell polyoma virus (MCPyV), has been identfed as the responsible

agent. Antcipatng that cross reactvity on immunohistochemistry might exist

between (TSPyV) and other polyoma viruses, we stained our case for both SV40

and MCPyV, but both proved negatve.

P851BENIGN PIGMENTED PURPURIC DERMATOSES: GRANULOMATOUS VARIANT.

E. MacQuarrie, S. Pasternak, M, Torok, S. Veerassamy, N. Walsh. Department of

Pathology, QEII Health Sciences Center and Dalhousie University, Halifax, Nova

Scota.

The benign pigmented purpuric dermatoses (BPPD) are a spectrum of

dermatologic disorders characterized by petechial and pigmented macules usually

confned to the lower limbs. Their etology is unknown and several clinical variants

are recognized. At the microscopic level they are characterized by angiocentric

lymphocytc infammaton, red blood cell extravasaton and hemosiderin

depositon. A granulomatous variant of the BPPD has recently been described and

to date 9 cases have been reported in the literature. In contrast to the

conventonal type, this variant is characterized histopathologically by ill-defned,

non-necrotzing granulomata admixed with the lymphocytc infammatory

background. Although initally the granulomatous variant of the BPPD was

thought to occur only in Asian patents, this racial predilecton has not been

substantated. A tenuous associaton with hyperlipidemia has been noted but this

requires further study. The principal importance of recognizing this entty lies in

the need to include it in the histopathological diferental diagnosis of

granulomatous dermal infltrates. W e report here two additonal patents with

the granulomatous variant of BPPD and elaborate on this entty in the context of

existng informaton in the literature.

P852AN EARLY INVASIVE SQUAMOUS CELL CA ARISING IN A PROLIFERATING

EPIDERMAL CYST.

D. El Demellawy1,2, S. Tauqir3, S. Alowami3. Pathology Departments: 1Northern

Ontario School of Medicine, Sudbury, Ontario; 2William Osler Health Center,

Brampton, Ontario; 3McMaster University, Hamilton, Ontario.

In contrast to cutaneous epidermal cysts, neoplastc transformaton of their

epithelium is extremely rare. We report a 48 year old lady presents with a growing

skin nodule in her right forearm. The lesion measures 2.8 cm in maximum

dimension. The patent has no other relevant medical history. The lesion is

excised. Microscopically a rare squamous cell carcinoma arising in the wall of an

otherwise conventonal epidermal cyst is identfed. The cyst show preserved

granular cell layer with few areas of squamous proliferaton. No evidence of

abrupt keratnisaton. The cyst has no evidence of epidermal connecton despite

examinaton in total and examinaton of multple levels. No evidence of

recurrence during the 2 year of follow up period. We present a rare case of early

invasive squamous cell carcinoma arising from proliferatng epidermal cyst, with

emphasis on enttes that may overlap morphologically and represent diagnostc

pitalls.

P853INFILTRATIVE AMELANOTIC/HYPOMELANOTIC CELLULAR BLUE NEVUS: AN

UNDESCRIBED VARIANT OF BLUE NEVUS.

A. Mishra1, D. Ghazarian2, A. Al Habeeb2, S. Sade3. 1Department of Laboratory

Medicine and Pathobiology, University of Toronto, Toronto, Ontario; 2Department

of Pathology, Toronto General Hospital, University of Toronto, Toronto, Ontario; 3Department of Pathology, Sunnybrook Health Sciences Centre, University of

Toronto, Toronto, Ontario.

Amelanotc/hypopigmented blue nevi are rare lesions that occur in both sexes,

though more commonly in females. These have a wide age distributon with a

predilecton for young individuals. The histologic diagnosis of

amelanotc/hypopigmented blue nevus (loss of melanin pigment in 95% of the

lesion) hinges upon the recogniton of typical architectural and cytological

features of a cellular blue nevus and the exclusion of other tumors. We report

two cases of a hitherto unreported variant of hypopigmented blue nevi, the

‘Infltratve Amelanotc/Hypomelanotc Cellular Blue Nevus.’ These highly

infltratve and difuse lesions recur afer considerable tme. The exact biologic

potental of these lesions remain undetermined. The lesions could not be

completely excised in our patents despite multple excisions and our patents

contnue to be closely followed. These recurrent infltratve

hypopigmented/amelanotc cellular blue nevi, afectng young patents can be

easily confused with other lesions like: fbromatosis, dermatofbroma, malignant

blue nevus (blue nevus like melanoma), desmoplastc melanoma, cellular

neurothekoma and clear cell sarcoma. Recogniton of this entty is important to

foster appropriate diagnosis, and case reportng is essental to determine the

exact nature and outcome of these lesions. Herein, we report two cases of

Infltratve Amelanotc/Hypomelanotc Blue Nevi and discuss treatment

approaches and follow-up data.

23

P854NEW MOLECULAR GRADING FOR SQUAMOUS CELL CARCINOMA SKIN.

M.H. Bukhari, R. Ali, A. Nasir, S. Niazi, S. Bashir.

Background: The study was conducted to suggest a new molecular grading

technique that may predict the risk of disease recurrence as well as potental

chemotherapy beneft that may promise in refning clinical decision making.

Materials and Methods: Scoring for histology, staging, Ki-67 index and p53

protein expression was performed on 180 samples of squamous cell carcinoma.

Data regarding pathologic prognostc factors e.g, lymph node metastasis, local

invasion, distant metastasis, recurrence and 5 years survival was also collected for

each case. Results: SCC was designated low, intermediate, and high trade grades

based on the sum of point values assigned to each 4 scores of histological

diferentaton, staging, p53 protein expression and Ki-67 index. Expression of P53

was found to be related to the Ki-67 with the scores of histology and stages of

SCC. A poor correlaton was found between the conventonal histological grades

(i.e. Spearman correlaton=0.928) but a positve correlaton was seen in the

surgical stages (i.e. Spearman correlaton= 0.721). A signifcant correlaton was

also seen with disease outcome like local invasion, lymph node involvement,

distance metastasis (Kendall’s Tau-b=0.394;p-value=0.00 ) and recurrence

(Kendall’s Tau – b= -0.966, p-value=0.025). Conclusion: Molecular grading system

indicates a ternary grading scheme for SCC. This practcal approach has potental

to improve clinical evaluaton of SCC in understanding the pathologic and clinical

behavior of SCC.

P855GIANT CELL TEMPORAL ARTERY ARTERITIS ASSOCIATED WITH BASAL CELL

CARCINOMA: COINCIDENCE OR CONNECTION?

D. El Demellawy MBBCh, PhD FRCPC1,2, A. Bane MBBCh, PhD, FRCpath, E. Mahe

BSc, MD 3 , S. Alowami MBBCh, FCAP, FRCPC3. 1Department of Pathology and

Laboratory Medicine, William Osler Health Care, Brampton, Ontario; 2Northern

Ontario School of Medicine, Sudbury, Ontario; 3Department of Pathology &

Molecular Medicine, McMaster University, Hamilton, Ontario.

Giant cell arterits is a granulomatous vasculits of large and medium sized

arterites manifestng as temporal arterits and/or polymyalgia rheumatca. The

histological assessment of temporal artery biopsies is frequently encountered in

anatomical pathology and has important diagnostc consequences in patents

clinically suspected of having giant cell arterits. In additon to the morbidity

directly atributable to giant cell arterits, there is ongoing debate in the literature

regarding a potental associaton between giant cell arterits and various

malignancies. We present a case of an 83 year old male presentng with an

ulceratng lef temporal lesions clinically suspected to be a basal cell carcinoma.

Upon histologic interpretaton of the primary excision specimen, a focus of large

vessel giant cell arterits was identfed immediately deep to the basal carcinoma

in queston. This unique case serves to reinforce the importance of careful

histological examinaton of tssue received by the pathology department in order

that an otherwise occult disease process with important clinical consequences is

not overlooked. We also present a review of the literature highlightng the

contnuing debate over the potental associaton of giant cell arterits with the

development of a malignancy.

24